胰岛素样生长因子-Ⅰ在奶牛骨代谢病中的作用及机制
|
摘要
奶牛骨代谢性疾病(bone metabolic disease,BMD)是包括软骨症、佝偻病、产后瘫痪、产褥热等一系列由钙磷代谢紊乱引起的营养代谢病。胰岛素样生长因子(insulin-like growth factor,IGF)-I是骨骼生长和矿化中钙磷代谢调节的关键因子,人类临床研究表明其与骨代谢性疾病密切相关。本研究从下述四个方面探讨IGF-I对奶牛骨代谢病中的影响及其机制。
1.奶牛血浆IGF-I的测定及其与骨代谢相关因子的关系
设计了三个独立的试验以探讨IGF-I与奶牛钙磷代谢相关因子的关系。试验I检测不同泌乳阶段钙、磷、IGF-I、甲状旁腺激素(parathyroid hormone,PTH)、降钙素(calcitionin,CT)等骨代谢相关因子水平,试验Ⅱ检测不同年龄奶牛骨代谢相关因子水平,试验Ⅲ检测奶牛骨代谢病与相关因子的关系。结果显示,奶牛年龄、妊娠状况及血浆IGF-I、PTH、CT水平与机体钙磷水平密切相关,血浆Ca、IGF-I、P、ALP、PTH水平与骨代谢性疾病相关,此外IGF-I与Ca、P正相关(r=0.390,P=0.049;r=0.359,P=0.044),PTH负相关(r=—0.790,P=0.002)。提示IGF-I与奶牛钙磷代谢密切相关,可以作为诊断奶牛骨代谢病的特异生化标志物。
2.奶牛成骨细胞的体外培养、鉴定及生物特性研究
采用胰蛋白酶-组织块移性法获取的细胞具有典型的成骨细胞形态和特性:ALP染色呈阳性,活性水平较高;培养7d后可检测到OC mRNA表达,12d后细胞上清液中可检测到OC蛋白;诱导培养2w后细胞可形成钙化结节。提示本实验室建立的方法所培养的细胞具有成骨细胞特性,可获得高纯度、高活性的奶牛成骨细胞。
3.IGF-I对奶牛成骨细胞增殖、分化、矿化及重建的影响
研究外源性IGF-I对体外培养的奶牛成骨细胞增殖、分化、矿化及重建的影响。结果显示,1-200ng/mL IGF-I均能促进奶牛成骨细胞增殖,100ng/mL组具有最大刺激效应,且IGF-I干预组细胞光密度值(optical density value,OD)从第1d到第5d逐渐增加,第7d降低。与对照组相比,10ng/mL与100ng/mL IGF-I均可显著诱导ALP活性、OC水平以及基质钙含量,钙化结节数量增加20%-180%(P＜0.05或P＜0.01)。半定量RT-PCR结果显示:10、50、100ng/mL IGF-I干预5d OPG/β-actin、RANKL/β-actin比值显著高于0ng/mL组(P＜0.05);ELISA显示,在1-100ng/mL浓度范围内,IGF-I呈剂量依赖方式上调OPG蛋白表达,其中10、50、100ng/mL干预组与0ng/mL组差异显著(P＜0.05)。提示IGF-I是奶牛成骨细胞增殖、分化以、矿化及重建的代谢促进剂,这可能是IGF-I参与奶牛骨代谢性疾病的重要机制之一。
4.IGF-I抑制血清饥饿诱导的奶牛成骨细胞凋亡
研究血清饥饿对奶牛成骨细胞凋亡的诱导作用,并探讨IGF-I对血清饥饿诱导的奶牛成骨细胞的影响。结果显示,10~(-3) M脱氧胸苷存在时,血清饥饿2d,MTT法检测到细胞存活率为50%,经琼脂糖凝胶电泳可见梯形凋亡条带。流式细胞术分析显示,与血清饥饿组相比,100ng/mL IGF-I显著增高奶牛成骨细胞的增殖指数,降低其凋亡率(P＜0.01)。Caspase-3检测结果显示IGF-I显著抑制csspsse-3的活性(P＜0.05)。结果提示血清饥饿可诱导奶牛成骨细胞凋亡,IGF-I抑制这种凋亡诱导作用。
Metabolic bone disease, which includes a number of disorders related to the weakening of the bone or impaired regulatory function, is caused by an imbalance in calcium and phosphorus, with a ratio that normally strongly favours an excess of phosphorus. Insulin-like growth factor-I (IGF-1) exert important role in the growth and mineralisation in bone. And it showed correction with the bone metabolic disease from the human clinical date. We hypothesed that IGF-I will exert important effect on metabolic bone disease of dairy cows. Four relative experiments were desiged here toevaluate this effect.
1. The relationship of IGF-I and bone metabolism related factors on Chinese Holstein
The aim of the study was to evaluate the relationship of insulin-like growth factor-I and bone metabolism related factors on Chinese Holstein. Three independent experiments were designed. Experiment I was to detect the level of calcium (Ca), phosphorus (P), parathyriod hormone (PTH), calcitionin (CT) and alkaline phosphatase (ALP) in cows with different age. Experiment II was to detect the level of these indexs in the ones in different lactation stage. And experiment III detected these indexs in health cows and the ones with bone metabolic disease. The results showed that age, the lactation stage, the level of IGF-I, PTH and CT were related to Ca and P metabolism in dairy cows. Serum level of Ca、IGF-1、P、ALP、PTH all showed correction with the bone metabolic disease of cows. And Ca and P showed positive correction with IGF-I, while PTH showed the opposite correction. It could be conclude that IGF-I was corrected to Ca and P metabolim in dairy cattle, and could be used as a marker of bone metabolic disease in cows
2. Culture and identification of dairy cattle osteoblasts and its biological characteristic
Osteoblastic cells were isolated by trypsin digestion method here. Cells liberated from the bone fragments and adhered on the bottom of the culture flask after 7 days of culture. At the 14~(th) days'culture, the number of osteoblasts reached the highest level, and the cells had grown to confluence. Cells in culture exhibited ALP activity and were positive to OC in supernate at the 12~(th) day. The expression of osteocalcin mRNA can be detected with RT-PCR at the 7th day. The results showed that the cells isolated and cultured in this experiment possessed the properties of osteoblast. Pure and active dairy cattle osteoblasts can be obtained by the technique established in this study.
3. The stimulatory effect of IGF-I on the proliferation, differentiation, mineralisation, and remodeling of osteoblastic cells from Holstein cattle
This study investigated the effect of exogenous IGF-I on the proliferation and differentiation of osteoblastic cells from Chinese Holstein cattle and the resultant bone-nodule formation and mineralisation in vitro. The MTT assay showed that cell proliferation in the cultures was stimulated by IGF-I at concentrations ranging from 1-200ng/mL, with the maximum effect observed at 100ng/mL. This effect was observed from day 1 and peaked at day 5, but decreased at day 7. At concentrations of 10ng/mL and 100ng/mL, IGF-I significantly induced ALP activity, OC level, matrix calcium content, and nodule formation of the osteoblastic cells by 20% to 180% (P < 0.05 or P < 0.01), compared to the controls. The results by semiquantitive RT-PCR demonstrated that IGF-I with 1-100ng/mL concentrations all showed stimulated RANKL and OPG mRNA expression. Compared with the 0ng/mL group, exposure to 10-100ng/mL groups presented significantly increased ration of OPG/β-actin、RANKL /β-actin, as well as the ration of OPG / RANKL (P < 0. 05). IGF-I ranging from 1-100ng/mL up-regulated OPG protein level in a dose-dependent manner by ELISA, and the 10-100ng/mL groups showed markly enhanced effect compared with 0ng/mL group (P < 0. 05). The results suggested that IGF-I is an anabolic agent for proliferation, differentiation, mineralisation and bone remodeling of dairy cow osteoblasts, and could therefore act as a potential treatment for the metabolic bone diseases in these animals.
4. Inhibitory effect of IGF-I on the cow osteoblasts apoptosis induced by serum starvation
The objective of this experiment investigate the effect of serum starvation on the apotosis of osteoblastic cells from Chinese Holstein cattle, and study the effect of IGF-I on this induction. Results showed that the treatment of serum starvation for 2d in the presence of 10~(-3) M thymidine induced the apoptosis of cow osteoblasts. In contast to serum starvation group, 100ng/mL IGF-I significantly increased proliferation index (P<0.01), and decreased apoptosis rate (P<0.01) by the Flow cytometry. And the activity of caspase-3 was inhibited by 100ng/mL IGF-I. It suggested that osteoblastic cells from Chinese Holstein cattle could be apoptosed induced by serum starvation for 2d, and IGF-I inhibited this apotosis process.
1.奶牛血浆IGF-I的测定及其与骨代谢相关因子的关系
设计了三个独立的试验以探讨IGF-I与奶牛钙磷代谢相关因子的关系。试验I检测不同泌乳阶段钙、磷、IGF-I、甲状旁腺激素(parathyroid hormone,PTH)、降钙素(calcitionin,CT)等骨代谢相关因子水平,试验Ⅱ检测不同年龄奶牛骨代谢相关因子水平,试验Ⅲ检测奶牛骨代谢病与相关因子的关系。结果显示,奶牛年龄、妊娠状况及血浆IGF-I、PTH、CT水平与机体钙磷水平密切相关,血浆Ca、IGF-I、P、ALP、PTH水平与骨代谢性疾病相关,此外IGF-I与Ca、P正相关(r=0.390,P=0.049;r=0.359,P=0.044),PTH负相关(r=—0.790,P=0.002)。提示IGF-I与奶牛钙磷代谢密切相关,可以作为诊断奶牛骨代谢病的特异生化标志物。
2.奶牛成骨细胞的体外培养、鉴定及生物特性研究
采用胰蛋白酶-组织块移性法获取的细胞具有典型的成骨细胞形态和特性:ALP染色呈阳性,活性水平较高;培养7d后可检测到OC mRNA表达,12d后细胞上清液中可检测到OC蛋白;诱导培养2w后细胞可形成钙化结节。提示本实验室建立的方法所培养的细胞具有成骨细胞特性,可获得高纯度、高活性的奶牛成骨细胞。
3.IGF-I对奶牛成骨细胞增殖、分化、矿化及重建的影响
研究外源性IGF-I对体外培养的奶牛成骨细胞增殖、分化、矿化及重建的影响。结果显示,1-200ng/mL IGF-I均能促进奶牛成骨细胞增殖,100ng/mL组具有最大刺激效应,且IGF-I干预组细胞光密度值(optical density value,OD)从第1d到第5d逐渐增加,第7d降低。与对照组相比,10ng/mL与100ng/mL IGF-I均可显著诱导ALP活性、OC水平以及基质钙含量,钙化结节数量增加20%-180%(P＜0.05或P＜0.01)。半定量RT-PCR结果显示:10、50、100ng/mL IGF-I干预5d OPG/β-actin、RANKL/β-actin比值显著高于0ng/mL组(P＜0.05);ELISA显示,在1-100ng/mL浓度范围内,IGF-I呈剂量依赖方式上调OPG蛋白表达,其中10、50、100ng/mL干预组与0ng/mL组差异显著(P＜0.05)。提示IGF-I是奶牛成骨细胞增殖、分化以、矿化及重建的代谢促进剂,这可能是IGF-I参与奶牛骨代谢性疾病的重要机制之一。
4.IGF-I抑制血清饥饿诱导的奶牛成骨细胞凋亡
研究血清饥饿对奶牛成骨细胞凋亡的诱导作用,并探讨IGF-I对血清饥饿诱导的奶牛成骨细胞的影响。结果显示,10~(-3) M脱氧胸苷存在时,血清饥饿2d,MTT法检测到细胞存活率为50%,经琼脂糖凝胶电泳可见梯形凋亡条带。流式细胞术分析显示,与血清饥饿组相比,100ng/mL IGF-I显著增高奶牛成骨细胞的增殖指数,降低其凋亡率(P＜0.01)。Caspase-3检测结果显示IGF-I显著抑制csspsse-3的活性(P＜0.05)。结果提示血清饥饿可诱导奶牛成骨细胞凋亡,IGF-I抑制这种凋亡诱导作用。
Metabolic bone disease, which includes a number of disorders related to the weakening of the bone or impaired regulatory function, is caused by an imbalance in calcium and phosphorus, with a ratio that normally strongly favours an excess of phosphorus. Insulin-like growth factor-I (IGF-1) exert important role in the growth and mineralisation in bone. And it showed correction with the bone metabolic disease from the human clinical date. We hypothesed that IGF-I will exert important effect on metabolic bone disease of dairy cows. Four relative experiments were desiged here toevaluate this effect.
1. The relationship of IGF-I and bone metabolism related factors on Chinese Holstein
The aim of the study was to evaluate the relationship of insulin-like growth factor-I and bone metabolism related factors on Chinese Holstein. Three independent experiments were designed. Experiment I was to detect the level of calcium (Ca), phosphorus (P), parathyriod hormone (PTH), calcitionin (CT) and alkaline phosphatase (ALP) in cows with different age. Experiment II was to detect the level of these indexs in the ones in different lactation stage. And experiment III detected these indexs in health cows and the ones with bone metabolic disease. The results showed that age, the lactation stage, the level of IGF-I, PTH and CT were related to Ca and P metabolism in dairy cows. Serum level of Ca、IGF-1、P、ALP、PTH all showed correction with the bone metabolic disease of cows. And Ca and P showed positive correction with IGF-I, while PTH showed the opposite correction. It could be conclude that IGF-I was corrected to Ca and P metabolim in dairy cattle, and could be used as a marker of bone metabolic disease in cows
2. Culture and identification of dairy cattle osteoblasts and its biological characteristic
Osteoblastic cells were isolated by trypsin digestion method here. Cells liberated from the bone fragments and adhered on the bottom of the culture flask after 7 days of culture. At the 14~(th) days'culture, the number of osteoblasts reached the highest level, and the cells had grown to confluence. Cells in culture exhibited ALP activity and were positive to OC in supernate at the 12~(th) day. The expression of osteocalcin mRNA can be detected with RT-PCR at the 7th day. The results showed that the cells isolated and cultured in this experiment possessed the properties of osteoblast. Pure and active dairy cattle osteoblasts can be obtained by the technique established in this study.
3. The stimulatory effect of IGF-I on the proliferation, differentiation, mineralisation, and remodeling of osteoblastic cells from Holstein cattle
This study investigated the effect of exogenous IGF-I on the proliferation and differentiation of osteoblastic cells from Chinese Holstein cattle and the resultant bone-nodule formation and mineralisation in vitro. The MTT assay showed that cell proliferation in the cultures was stimulated by IGF-I at concentrations ranging from 1-200ng/mL, with the maximum effect observed at 100ng/mL. This effect was observed from day 1 and peaked at day 5, but decreased at day 7. At concentrations of 10ng/mL and 100ng/mL, IGF-I significantly induced ALP activity, OC level, matrix calcium content, and nodule formation of the osteoblastic cells by 20% to 180% (P < 0.05 or P < 0.01), compared to the controls. The results by semiquantitive RT-PCR demonstrated that IGF-I with 1-100ng/mL concentrations all showed stimulated RANKL and OPG mRNA expression. Compared with the 0ng/mL group, exposure to 10-100ng/mL groups presented significantly increased ration of OPG/β-actin、RANKL /β-actin, as well as the ration of OPG / RANKL (P < 0. 05). IGF-I ranging from 1-100ng/mL up-regulated OPG protein level in a dose-dependent manner by ELISA, and the 10-100ng/mL groups showed markly enhanced effect compared with 0ng/mL group (P < 0. 05). The results suggested that IGF-I is an anabolic agent for proliferation, differentiation, mineralisation and bone remodeling of dairy cow osteoblasts, and could therefore act as a potential treatment for the metabolic bone diseases in these animals.
4. Inhibitory effect of IGF-I on the cow osteoblasts apoptosis induced by serum starvation
The objective of this experiment investigate the effect of serum starvation on the apotosis of osteoblastic cells from Chinese Holstein cattle, and study the effect of IGF-I on this induction. Results showed that the treatment of serum starvation for 2d in the presence of 10~(-3) M thymidine induced the apoptosis of cow osteoblasts. In contast to serum starvation group, 100ng/mL IGF-I significantly increased proliferation index (P<0.01), and decreased apoptosis rate (P<0.01) by the Flow cytometry. And the activity of caspase-3 was inhibited by 100ng/mL IGF-I. It suggested that osteoblastic cells from Chinese Holstein cattle could be apoptosed induced by serum starvation for 2d, and IGF-I inhibited this apotosis process.
引文
1.单鹏飞.新一代骨代谢生化标志物的临床应用.国外医学内分泌学分册,2003,23:259-262.
2.姜华,王稚英,姚琦,张立海.缺氧对成骨细胞增殖及凋亡的影响.口腔颌面修复学杂志,2005,5:81-83.
3.刘彬,丁卫,谷静丽,葛韵琴,杜国光.EGF及IGF-I对UMR106细胞增殖及β-微管蛋白表达的影响.生物化学杂志,1995,11:406-41.
4.刘根桃,陈伟华,郑元林等.胰岛素养生长-1的放射免疫测定方法的建立.南京农业大学学报,1999,22:63-66.
5.刘真喜,傅焕,赵彤.IGF-1与细胞凋亡的研究进展.医学综述,2001,10:579-580.
6.刘忠厚主编.骨质疏松学.北京:科学出版社,1998,91-93.
7.石义刚,陶天遵,陶树清,刘枫晨,徐强,王立春,吉光荣,吴丽萍.rhIGF-1对成骨细胞增殖、分化及骨保护素、骨保护素配体基因mRNA表达的影响.中国骨质疏松杂志,2003,9:31-34.
8.斯佩克特D L.细胞实验指南.黄培堂译.北京:科学出版社,2001,93-98.
9.宋爱梅,束蓉.体外培养骨髓间充质干细胞向成骨细胞分化的影响因素研究.牙体牙髓牙周病学杂志,2005,15:55.
10.孙玉芳.奶牛血清碱性磷酸酶及钙磷含量的测定与分析.中国奶牛,1996,6:12.
11.唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量的测定.中国兽医科技,2002,32:26-28.
12.唐孝明,裴福兴,沈彬,刘仲前,张耀明,庞健.雌激素对血清饥饿诱导成骨细胞凋亡的影响.中国康复理论与实践,2006,12:123-125.
13.王九峰,金久善,夏兆飞,朱要宏.骨钙素在乳牛骨软病研究上的重要性.畜牧兽医学报,1999,30:513-518.
14.王卫华,于世凤.成骨细胞体外培养方法研究进展.国外医学口腔医学分册,1996,23:287-291.
15.王智兴,李群,张玥,朱亚萍.成骨生长肽对成骨细胞样细胞的分化和成骨作用.上海第二医科大学学报,2000,20:227-229.
16.徐成丽,鄢盛恺,祖淑玉,沈瑛,翟凤英,韩少梅,张李伟,朱广瑾.2342例北京地区儿童血清钙、无机磷水平检测分析.中国医学科学院学报,2004,26:455-459.
17.徐萍,张克勤,刘超,刘翠萍,唐伟.重组人胰岛素样生长因子I对大鼠成骨细胞增殖、凋亡及I型胶原蛋白合成的影响.中国骨质疏松杂志,2006,12:17-21.
18.杨景山.医学细胞化学与细胞生物技术.北京:北京医科大学,中国协和医院大学联合出版社,1990,42.
19.余增丽,韩萍,李文杰.染料木黄酮对人成骨细胞凋亡的影响.营养学报,2004,26:288-291.
20.曾晓峰,赵建宁.骨保护素及其配体对破骨细胞功能的调控作用.中国矫形外科杂志,2004,12:463-465.
21.翟中和,王喜忠,丁明孝.细胞生物学.北京:高等教育出版社,2000,357-360.
22.张吉富.测骨矿物质含量诊断奶牛钙磷代谢障碍.中国兽医科技,1993,23:33-34.
23.张明,金惠铭,曹翔,刘清行,钱睿哲,张国平.低浓度H_2O_2对肺微血管内皮细胞的迟发效应-凋亡.中国病理生理杂志,1999,15:28.
24.张兴凯,杨庆铭,邓廉夫,朱雅萍.成人成骨细胞体外培养.中华外科杂志,2000,38:51-53.
25.张玉静.分子遗传学.北京:科学出版社,2000,27.
26.郑晓辉,方秀斌.骨钙素的基础与应用研究进展.解剖科学进展,1999,4:327-329.
27.周洪涛,李风洲,宁自利.乳牛血清钙磷乘积与骨密度的关系.黑龙江畜牧兽医,1996,1:6-7.
28.朱新民,王加启.奶牛钙磷代谢的常见问题及其机理.中国畜牧兽医,2005,13:23-25.
29.左爱仁,范青生.细胞凋亡及其机制的研究.生物学教学,2003,6(28):7-9.
30. Aarskog D, Aksnes L. Acute response of plasma 1,25-dihydroxyvitamin D to parathyroid hormone. Lancet, 1980, 16: 362-363.
31. Calo L, Castrigano R, Davis P A. Role of insulin-like growth factor-I in primary osteoporosis: a correlative study. J Endocrionl invest, 2000,23: 223-237.
32. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, Yoshiki S, Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D_3. Proc Natl Acad Sci, 1981, 78: 4990-4994.
33. Alborzi A, Mac K, Glackin CA, Murray S S, Zernik, JH. Endochondral and intramembranous fetal bone development: osteoblastic cell proliferation and expression of alkaline phosphatese, M-twist, and histone H4. J Craniofac Genet Dev Biol, 1996, 16:94-106.
34. Atkins G J, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdoliou A, Harrison K, Findlay D M, Zannettino A C. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res, 2003, 18: 1008-1098.
35. Barton B A, Hodnett D W, Jorgensen N A, DeLuca H F. 24,25-Dihydroxyvitamin D_3 administration increases incidence of parturient paresis. J Dairy Sci, 1984, 67: 1236-1239.
36. Barton B, Jorgensen A N A, Horst R L, DeLuca H F. Influence of dietary phosphorus level on the concentration of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, calcium and phosphorus in plasma of aged dairy cows. J Dairy Sci, 1978, 61: 145 (Abstract).
37. Bautista C M, Mohan S, Baylink D J. Insulin-like growth factor- I and II arepresent in the skeletal tissues of ten vertebrates. Metabolism, 1990, 39: 96-100.
38. Baxter R C. Molecular aspects of insulin-like growth factor binding proteins. In: LeRoith D ed., Advances in Molecular and Cellular Endocrinology. Greenwich: JAI Press, 1997. Vol 1,123-159. .
39. Baxter R C. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab, 2000, 278: E967-76.
40. Bellows C G, Aubin J E, Heersche J N M, Antosz M E. Mineralised bone nodules formed in vitro from enzymatically released rat calvaria cell populations. Calcif Tissue Int, 1986,38:143-437.
41. Bing 0 H L. Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure over-load. J Mol Cell Cardiol, 1994, 26: 943-948.
42. Bordier P, Rasmussen H, Marie P, Miravet L, Gueris J, Ryckwaert A. Vitamin D metabolite and bone mobilization in man. J Clin Endocrinol Metab, 1978, 46: 284-294.
43. Bourrin S, Ammann P, Bonjour J P, Rizzoli R. Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats. Endocrinology, 2000, 141:3149-3155.
44. Braithwaite G D. Calcium and phosphorus metabolism in ruminants with special reference to parturient paresis. J Dairy Res, 1976,43: 501-520.
45. Braithwaite G D. Calcium and phosphorus requirements of the ewe during pregnancy and lactation. 2. Phosphorus. Br J Nutr, 1983, 50: 723-736.
46. Broadus A E, Horst R L, Lang R, Littledike E T, Rasmussen H. The importance of circulating 1,25-dihydroxyvitamin D in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. N Engl J Med, 1980, 302: 421-426.
47. Campbell P I, Breedlove D K, Kempson S A. Insulin-like growth factor I stimulates sodium-phosphate cotransport in the rat oeteoblastic cell line UMR-106-01. Am J Physiol, 1992,262: E389-93.
48. Canalis E, McCarthy T, Centrella M. Isolation of growth factors from adult bovine bone. Calcif Tissue Int, 1988,143, 346-351.
49. Canterbury J M, Lerman S, Claflin A J, Henry H, Norman A, Reiss E. Inhibition of parathyroid hormone secretion by 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol in the dog. J Clin Invest, 1978, 61: 1375-1383.
50. Care A D, Barlet J P, Abdel-Hafeez H M. Calcium and phosphate homeostasis in ruminants and its relationship to the actiology and prevention of parturient paresis. In: Ruckebusch Y, Thivend D ed., Digestive physiology and metabolism in ruminants. Westport CT: AVI Publ Co., Inc., 1980. 429-445.
51. Celiker R, Arslan S. Comparison of serum insulin-like growth factor-1 and growth hormone levels in osteoporotic and non-osteoporotic postmenopausal women. Rheumatol Int, 2000, 19: 205-208.
52. Chang Y L, Stanford C M, Keller J C. Calcium and phosphate supplementation promotes bone cell mineralisation: implications for hydroxyapatite (HA)-enhanced bone formation. J Biomed Mater Res, 2000, 52: 270-278.
53. Clark R. A study of the water-soluble phosphate concentration of the ruminal contents in normal and phosphorus deficient animals. Onderstepoort J Vet Res, 1953.26:137.
54. Cohen R D H. Phosphorus in rangeland ruminant nutrition: A review. Livestock Prod Sci, 1980,7:25-37.
55. Collignon H, Davicco M J, Barlet J P. Isolation of cells from ovine fetal long bone and characterization of their osteoblastic activities during in vitro mineralization. Arc of Physics and Biochemistry, 1997, 105: 158-166.
56. Colovos N F, Keener H A, Davis H A. Effect of pulverized limestone and calcium phosphate on the nutritive value of dairy cattle feed. J Dairy Sci, 1958, 41: 676.
57. Curtis C R, Erb H N, Smiffen G J, Smith R D, Powers P A, Smith M C, White M E, Hillman R B, Pearson E J. Association of parturient hypocalcemia with periparturient disorders in Holstein cows. J Am Vet Med Assoc, 1983, 183: 559-561.
58. Davicco M J, Remond B, Jabet S, Barlet J P. Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period. Reprod Nutr Dev, 1992,32,313-319.
59. Dclany A M, Rydzicl S, Canalis E. Autocrine down-regulation of collagenase-3 in rat bone cell culture by insulin-like growth factor. Endocrinology, 1996, 137: 4665-4670.
60. Delany A M, Pash J M. Canalis E. Cellular and clinical per-spectives on skeletal insulin-like growth factor I. J Cell Biochem, 1994, 55: 328-333.
61. DeLuca H F. Recent advances in the metabolism of vitamin D. Ann Rev Physiol, 1981,43: 199-209.
62. Doleze I J. Flow cytometetry analysis of nuclear DNA content in higher plants. Phytochem Anal, 1991,2: 143-154.
63. Dulak N, Temin H. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication stimulating activity for embryo fibroblasts. J Cell Physiol, 1973,81:153-160.
64. Ernst M, Rodan G A. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone(GH): positive correlation with the presence of the GH-induced IGF- binding protein BP-3. Endocrinology 1990,127:807-814.
65. Ernst M, Rodan G A. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3. Endocrinology, 1990, 127: 807-814.
66. Fiedler J, Brill C, Blum W F, Brenner R E. IGF-1 and IGF-2 stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Bio Biophysical Res Communications, 2006, 345: 1177-1183.
67. Froesch E R, Burgi H, Ramseier E B, Bally P, Labhart A. Antibody suppressible and non-suppressible insulin-like activities in human serum and their physiological significance. J Clin Invest, 1963. 42:1816-1834.
68. Galbraith D W, Harkins K R, Maddox J M. Rapid cycle in intact plant tissue. Science, 1983,220:1049-1051.
69. Gallagher J C, Riggs B L, DeLuca H F. Effects of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab, 1980,51: 1359-1364.
70. Gast D R, Horst R L, Jorgensen N A, DeLuca H F. Potential use of 1,25-dihydroxyvitamin D_3 or prevention of parturient paresis. J Dairy Sci, 1979, 62: 1009-1013.
71. Gluckman P D, Douglas R G, Ambler G R, Breier B H, Hodgkinson S C, Koea J B, Shaw J H. The endocrine role of insulin-like growth factor I. Acta Paediatric Scand, 1991, 372(Suppl): 97-105.
72. Goad D L, Rubin J, Wang H, Tashjian A H Jr, Patterson C. Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I. Endocrinology, 1996, 137:2262-2268.
73. Goff J P. Calcium homeotasis challenged during lactation. Feedstuff's, 1989, 61: 29.
74. Goings R L, Jacobson N L, Beitz D C, Littledike E T, Wiggers K D. Prevention of parturient paresis by prepartum, calcium deficient diet. J Dairy Sci, 1974, 57: 1184-1188.
75. Grace N D, Ulyatt M J, MacRae J C. Quantitative digestion of fresh herbage by sheep. 3. Movement of Mg, Ca, P, K, and Na in digestive tract. J Agric Sci, 1974, 82:321.
76. Grace N D. Phosphorus kinetics in sheep. Br J Nutr, 1981,45:367.
77. Grant A B. Carotene: A rachitogenic factor in green feeds. Nature, 1953, 172: 627.
78. Gray R W. Control of plasma 1,25-(OH)_2 vitamin D concentrations by calcium and phosphorus in the rat: Effects of hypophysectomy. Calcif Tiss Int, 1981, 33: 485-488.
79. Green J, Goldberg R, Maor G PTH ameliorates acidosis-induced adverse effects in skeletal growth centers: the PTH-IGF-I axis. Kidney Int, 2003,63: 487-500.
80. Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab, 2002, 87: 2883-2891.
81. Hague A, Hicks D J, Bracey T S. Cell-cell contact amd specific cytokines inhibit apoptosis of colonic epithelial cells: growth factors protect against c-myc-independent apoptosis. BrJCancer, 1997, 75: 960-968.
82. Hanai Y, Tokuda H, Ishisaki A, Matsushima-Nishiwaki R, Nakamura N, Yoshida M, Takai S, Ohta T, Kozawa O. Involvement of p44/p42 MAP kinase in insulin-like growth factor-1 induced alkaline phosphatase activity in osteoblast-like-MC3T3-El cells. Mol Cell Endo, 2006,251: 42-48.
83. Hansard S L, Crowder H M, Lyke W A. The biological availability of calcium in feeds for cattle. J Anita Sci, 1957, 16:437-443.
84. Hayden J M, Mohan S. Baylink D J. The insulin-like growth-factor system and the coupling of formation to resorption. Bone, 1995, 17(2 Supply): 93S-98S.
85. He J, Rosen C J, Adams D J, Kream B E. Postnatal growth and bone mass in mice with IGF-1 haploinsufficiency. Bone, 2006, 38: 826-835.
86. Herault O, Domenech J, Georget M T. All-trans retinoic acid prevents apoptosis of human marrow CD~(34+) cells deprived of haematopoietic growth factors. Br J Haematology, 2002, 118: 289-295.
87. Hibbs J W, Pounden W D. Studies on milk fever in dairy cows. IV. Prevention by shorttime prepartum feeding of massive doses of vitamin D. J Dairy Sci, 1955, 38: 65-72.
88. Hibbs, J W, Conrad H R. The relation of calcium and phosphorus intake and digestion and the effects of vitamin D feeding on the utilization of calcium and phosphorus by lactating dairy cows. Ohio Agric Res Dev Ctr Res Bull, 1983, 150: 1-26.
89. Hill P A, lumber A, Meikle MC. Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology, 1997, 138: 3849-3858.
90. Hoffsis G F, Capen C C, Norman A W. The use of 1,25-dihydroxycholecalciferol in the prevention of parturient hypocalcemia in dairy cows. Bovine Pract, 1979, 13: 88.
91. Horst R L, Jorgensen N A, DeLuca H F. Plasma 1,25-dihydroxyvitamin D and parathyroid hormone levels in paretic dairy cows. Am J Physiol Gastrointest Liver Physiol, 1979a, 236: E634 (Abstract).
92. Horst R L, Jorgensen N A. Elevated plasma cortisol during induced and spontaneous hypocalcemia. J Dairy Sci, 1982, 65: 2332-2337.
93. Horst R L, Littledike E T. Comparison of plasma concentrations of vitamin D and its metabolite in young and aged domestic animals. Comp Biochem Physiol B, 1982, 73: 485-489.
94. Horst R L, Shepard R M, Jorgensen N A, DeLuca H F. The determination of vitamin D metabolites in a single plasma sample. Changes during parturition in dairy cows. Arch Biochem Biophys, 1979b, 192: 512-523.
95. Horst R W, DeLuca H F, Jorgenson N. Effect of age on calcium absorption and accumulation of 1,25-dihydroxyvitamin D_3 in intestinal mucosa of rats. Metab Bone Dis Rel Res, 1978,1: 29-34.
96. Hove K, Horst R L, Littledike E T, Beitz D C. Infusions of parathyroid hormone in ruminants: Hypercalcemia and reduced plasma 1,25-dihydroxyvitamin D concentrations. Endocrinology, 1984,114: 897-903.
97. Hsu Y L, Chang J K, Tsai C H, Chien T T, Kuo P L. Myricetin induces human osteoblast differentiation through bone morphogenetic protein-2/p38 mitogen-activated protein kinase pathway. Biochemical Pharmacology, 2007, 73: 504-514.
98. Iranmanesh A, Veldhuis J D. Clinical pathophysiology of the somatotropic (GH) axis in adults. Endocrinol Metab Clin North Am, 1992,21: 783-816.
99. Ishizuya T, Yokose S, Hori M. Parathyroid hormone exerts disparate effects on osteoblast differentiation on exposure time in rat osteoblastic cells. J Clin Inv, 1997,99:2961-2970.
100.Jasen M, Schaik F M A, Ricker A T, Bullock B, Woods D E, Gabbay K H, Nussbaum A L, Sussenbach J S, Van-Den-Brande J L. Sequence of cDNA encoding human insulin-like growth factor- I precursor. Nature, 1983, 306: 609-611.
101.Jia TL, Wang H Z, Xie L P, Wang X Y, Zhang R Q. Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production. Biochem Pharm, 2003,65: 709-715.
102.Jilka R L, Weinstein R S, Bellido T, Parfitt A M, Manolagas S C. Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res, 1998, 13: 793-802.
103.Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology, 1996, 137: 2187-2190.
104.Johansson A G, Lindh E, Ljunghall S. Insulin-like growth factor I stimulates bone turn over in osteoporosis. Lancet, 1992, 339: 1619.
105.Jonsson K B, Ljunghall S, Karlstrom O, Johansson A G, Mallmin H, Ljunggren O. Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts. Biosci Rep, 1993, 13: 297-302.
106.Jorgensen N A. Combating milk fever. J Dairy Sci, 1974, 57: 933-944.
107.Key L, Carnes D, Cole S, Holtrop M, Bar-Shavit Z, Shapiro F, Arceci R, Steinberg J, Gundberg C, Kahn A, Teitelbaum S, Anast C. Treatment of congenital osteopetrosis with high-dose calcitriol. N Engl J Med, 1984, 310: 409-415.
108.Kichura T S, Horst R L, Beitz D C, Littledike E T. Relationships between prepartal dietary calcium and phosphorus, vitamin D metabolism and parturient paresis in dairy cows.J Nutr,1982,112:480-487.
109.Kimura T,Majima Y,Guo Y,Yoshida T.The effect of growth factors on the proliferation and differentiation of human nasal gland cells.Arch Otolaryngol Head Neck Surg,2002,128:578-582.
110.Kong Y Y,Yoshida H,Sarosi I,Tan H L,Timms E,Cappareli C,Morony S,Oliveira-dos-Santos A J,Van G,Itie A,Khoo W,Wakenhan A,Dunstan C R,Lacey D L,Mak T W,Boyle W J,Penninger J M.OPGL is a key regulator of osteoclastogensi,lymphocyte development and lymph-node organogenesis.Nature,1999,397:315-323.
111.Kooijman R.Regulation of apoptosis by insulin-like growth factor(IGF)-I.Cytokine Growth Factor Rev,2006,17:305-323.
112.Kovacina K S,Steele-Perkins G,Roth R A.A role for the insulin-like growth factor Ⅱ/mannose-6-phosphate receptor in the insulin-induced inhibition of protein catabolism.Mol Endocrinol,1989,3:901-906.
113.Krook L,Lutwak L,McEntee K,Herrikson P A,Braun K,Roberts S.Nutritional hypercalcitonism in bulls.Cornell Vet,1971,61:625-639.
114.Kudo Y,Iwahita M,Takeda Y.Evidece for modu-lation of osteocalcin containing gamma-carboxyglutamic acid residues synthesis by insulin-like growth faxtor-I and vitamin K_2 in human osteosarcoma cell line MG-63.Eur J Endocrinol,1998,138:443-448.
115.Kudo Y,Iwashita M,Iguchi T,Takeda Y.The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells.Pflugers Arch,1996,432:419-426.
116.Kveiborg M,Flyvbjerg A,Eriksen E F,Kassem M.1,25-Dihydroxyvitamin D_3stimulates the production of insulin-like growth factor-binding proteins-2,-3 and -4 in human bone marrow stromal cells.Eur J Endocrinol,2001a,144:549-557.
117.Kveiborg M,Flyvbjerg A,Edksen E F,Kassem M.Transforming growth factor-β1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors.J Endocrinol,2001b,169:549-561.
118.Lacey D L,Tan H L,Lu J,Kaufman S,Van G,Qiu W,Rattan A,Scully S,Fletcher F,Juan T,Kelley M,Burgess T L,Boyle W J,Polverino A J. osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Amer J Pathology, 2000, 157: 435-448.
119.Langdahl B L, Kassem M, Moller M K, Eriksen E F. The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone. Eur J Clin Invest, 1998, 28: 176-183.
120.Lazowski D A, Fraher L J, Hodsman A, Steer B, Modrowski D, Han VK. Regional variation of insulin growth factor-I gene expression in mature rat bone and cartilage. Bone, 1994, 15: 563-576.
121.LeBlanc A C. Natural cellular inhibitors of caspases. Prog Neuropsychopharmacol Biol Psychiatry, 2003, 27: 215-229.
122.Leibholtz, J. Flow of calcium and phosphorus in digestive tract of sheep. Aust J Agric Res, 1974,25:147-154.
123.Li D W, Qin L L.. Effects of genistein on proliferation, differentiation, content of matrix calcium and mineralisation of cultured osteoblasts in vitro. Chin J Osteoporo, 2002, 8: 307-311.
124.Li Z X, Liu H M, Zhao D S. Diagnose and treatment of osteomalacia of dairy cow. Chin J Vet Med, 1996, 22: 27.
125.Lindsay R, Hart D M, Aitken J M,. Long-term prevention of postmenopausal osteoporosis by estrogen; Evidence for an increased bone mass after delayed onset of estrogentreatment. Lancet, 1986,1: 1038-1041.
126.Littledike E T, Horst R L. Inappropriate plasma 1,25-(OH)_2D response to parturient hypocalcemia in cows treated with vitamin D3, 1,25-(OH)_2D_3 or 1,25,26-(OH)_3D_3 prepartum.In: Norman A W, Schaefer K, Herrath D V, Grigoleit H G, eds., Vitamin D, chemical, biochemical and clinical endocrinology of metabolism. New York, NY: Walter de Gruyter, 1982. 475.
127.Lomba F, Chauvaux G, Teller E, Lengele R, Bienfet V. Calcium digestibility in cows as influenced by excess of alkaline ions over stable acid ions in their diets. Br J Nutr, 1978,39:425-429.
128.Louitit J F, Nisbet N W. The origin of osteoclasts, Immunobiology, 1982, 161: 193-203.
129.Ma Z J, Misawa H, Yamaguchi M. Stimulatory effect of zinc on insulin-like growth factor-I and transforming growth factor-beta production with bone growth of newborn rats. Int J MolMed, 2001, 8: 623-628.
130.Maccario M, Grottoli S, Camanni F. IGF-I levels in different conditions of low somatotrope secretion in adulthood:obesity in comparison with GH deficiency. Minerva Endocrinol, 1999,24: 57-61.
131.Mackie E J. Osteoblasts: novel roles in orchestration of skeletal architecture. International Joutnal of Biochemistry and Cell Biology, 2003, 35: 1301-1305.
132.Malpe R. Baylink D J. Linkhart T A, et al. Insulin growth factor(IGF)-I, -II, IGF binding proteins(IGFBP)-3f -4 and -5 levels in the conditioned media of normal human bone cells are skeletal site-dependent. J Bone Miner Res, 1997, 12: 423-30.
133.Malyszko J S, Wolczynski S, Mysliwiec M. Osteoprotegerin and its correlations with new markers of bone formation and bone resorption in kidney transplant recipients. Trans Proceedings, 2003, 35: 2227-2229.
134.Marie P. Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-beta. Rev Rhum Engl Ed, 1997,64: 44-53.
135.Marquardt J P, Holick M F, Horst R L, Jorgensen N A, DeLuca H F. Efficiency of 1α-hydroxyvitamin D_3 on prevention of parturient paresis. J Dairy Sci, 1974, 57: 606.
136.Marquardt J P, Horst R L, Jorgensen N A. Effect of parity on dry matter intake at parturition in dairy cattle. J Dairy Sci, 1977,60: 929-934.
137.Melissa K. Calcium metabolism and metabolic bone disease. Herp Care Collection, April, 2007. http://www.anapsid.org/mbd2.html 543(accessed 01.04.2007).
138.Middleton J, Arnott N, Walsh S. Osteoclasts in adult human osteophyte tissue express the mRNAs for IGF-1 and II and the type-Ⅰ IGF receptons. Bone, 1995, 16:287-293.
139.Mitsiades C S, Mitsiades N, Poulaki V, Schlossman R, Akiyama M, Chauhan D. Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications, Oncogene, 2002,21: 5673-5683.
140.Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, Tanaka K, Kumegawa M. Insulin-like growth factor-I supports formation and activation of osteoclasts. Endoceinology, 1992, 131:1075-1080.
141.Moe P W. Effects of level of intake on the utilization of diets by dairy cows. (Ph D thesis). Ithaca, NY: Cornetl Univ, 1965.
142.Murgo A J, Fried J, Burchenal D, Vale K L, Strife A, Woodcock T, Young C W, Clarkson B D. Effects of thymidine and thymidine plus 5-fluorouracil on the growth kinetics of a human lymphiod cell line. Cancer Res, 1980,40: 1543-1549.
143.Napoli J L, Sommerfeldt J L, Pramanik B C, Gardner R, Sherry A D, Partridge J J, Uskokovic M R, Horst R L. 19-Nor-10-ketovitamin D derivatives: Unique metabolites of vitamin D3, vitamin D2, and 25-hydroxyvitamin D3. Biochemistry, 1983. 22: 3636-3640.
144.Nasu M, Sugimoto T, Kaji H, Chihara K. Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5. Journal of Endocrinology, 2000, 167: 305-313.
145.National Research Council. Nutrient requirements of dairy cattle. 6th ed. Washington DC, 1978.
146.Norman A W. 1,25-Dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D_3: Key components of the vitamin D endocrine system. Contrib Nephrol, 1980, 18: 1-11.
147.OjO S A, Leipald H W, Cho D Y, Guffy M M. Osteopetrosis in two Hereford calves. J Am Vet Med Assoc, 1975, 166: 781-783.
148.01ney R C. Regulation of bone mass by growth hormone. Med Pediatr Oncol, 2003,41:228-234.
149.Olson W G, Jorgensen N A, Schultz L H, DeLuca H F. 1973. 25-Hydroxycholecalciferol (25-OHD_3) I. Treatment for parturient paresis. J Dairy Sci, 1973,56:885-888.
150.Ortiz C O, Chen B K, Bale LK, Overgaard M T, Oxvig C, Conover C A. Transforming growth factorbeta regulation of the insulin-like growth factor binding protein-4 protease system incultured human osteoblasts. J Bone Miner Res, 2003, 18: 1066-1072.
151.Palumbo C, Palazzini S, Marotti G. Morphological study of intercellular junctions during osteocyte differentiation. Bone, 1990,11: 401-406.
152.Panagakos F S. Insulin-like growth factors-I and-II stimulate chemotaxis of osteoblasts isolated from fetal rat calvaria. Biochimie, 1993, 75: 991-994.
153.Patel S, Lyons A R, Hosking D J. Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. Drugs, 1996,46: 594-617.
154.Pepene C E, Kasperk C H, Pfeilschifter J. Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro. Bone, 2001,29:540-546.
155.Peters M A, Lau E P, Snitman D L, Van W J, Underwood L E, Russel W E, Svoboda M E. Expression of a biologically active analogue of somatomedin-C/insulin-like growth factor-1. Gene, 1985, 35: 83-89.
156.Peterson W J. A method to assess the proliferating activity of small numbers of murine peripheral blood mononuclear cells. J Immunol Methods, 1987, 96: 171-176.
157.Poulaki V, Mitsiades C S, Kotoula V, Tseleni-Balafouta S, Ashkenazi A, Koutras D A. Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells, Am J Pathol, 2002, 161: 643-654.
158.Power R A, Iwaniec U T, Wronski T J. Changes in gene expression associated with the bone anabolic effects of basic fibroblast growth factor in aged ovariectomized rats. Bone, 2002, 31: 143-148.
159.Raile K, Hoflich A, Kessker U. Human osteosarcoma (U-2 OS) cells express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth- II /mannose-6 phosphate (IGF- II /M6P) receptors and synthesize IGF-I: Autocrine growth stimulation by IGF- II via the IGF-I receptor. J Cell Physiol, 1994, 159:531-541.
160.Ramberg C F, Johnson E K, Fargo R D, Kronfeld D S. Calcium homeostasis in cows with special reference to parturient hypocalcemia. Am J Physiol Regul Integr Comp Physiol, 1984,246: R698- R704.
161.Ramberg C F, Kronfeld D S, Wilson G D A. Regulation of calcium metabolism in cattle during growth, lactation, and change in diet. In: McDonald I W, Warner A C I eds., Digestion and metabolism in the ruminant. Armidale Aust: Univ New Engl Publ Unit, 1975.231-242.
162.Rinderknecht E, Humbel R E. Primary structure of human insulin-like growth factor- II. FEBS Lett, 1978a, 89: 283-286.
163.Rinderknecht E, Humbel R E. The amino acid sequence of human insulin-like factor- I and its structural homology with proinsulin. J Biol Chem, 1978b, 253: 2769-2776.
164.Robey P G, Termine J D. Human bone cells in vitro. Calcif Tissue Int, 1985, 37: 453-460.
165.Roth J A, Kaeberle M L. Effect of glucocorticoids on the bovine immune system. J Am Vet Med Assoc, 1982, 180: 894-901.
166.Rowland G N, Capen C C, Young D M, Black H E. Micrographic evaluation of bone from cows with experimental hypervitaminosis D, diet induced hypocalcemia, and naturally occurring parturient paresis. Calcif Tiss Res, 1972, 9: 179-193.
167.Rydziel S, Delany A M, Canalis E. Insulin-like growth factor I inhibits the transcription of collagenase 3 in osteoblast culture. J Cell Biochem, 1997, 67: 176-83.
168.Sachs M, Bar A, Cohen R, Mazur V, Mayer E, Hurwitz S. Use of 1α-hydroxycholecalciferol in prevention of bovine parturient paresis. Am J Vet Res, 1977, 38: 2039.
169.Salmon W D, Daughaday W H. A hormonally controlled serum factor which stimulates sulphate incorporation by cartilage in vivo. J Lab Clin Med, 1957, 49: 825-836.
170.Sara V R, Hall K. Insulin-like growth factors and their binding proteins. Physiol Reviews, 1990,70:591-614.
171.Scheven B A A, Hamilton N J, Fakkeldij T M V, Duursma S A. Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells. Growth Regul, 1991, 1: 160-167.
172.Seynaeve M, Janssens G, Hesta M, Van Nevel C, De Wilde R O. Effects of dietary Ca/P ratio, P level and microbial phytase supplementation on nutrient digestibilities in growing pigs: breakdown of phytic acid, partition of P and phytase activity along the intestinal tract. J Anim Physiol Anim Nutr, 2000, 83, 193-204.
173.Smith P N, Padilla M, Wasserman RH, Kallfelz F A. Calcium and 24,25-dihydroxyvitamin D: Inverse relation in cows with parturient paresis. Calcif Tiss Int, 1982,34: 564-566.
174.Smith V R, Merrill W G Parturient paresis. VII. A study of the leukocytes of cows with parturient paresis. J Dairy Sci, 1954, 37: 967-975.
175.Somjen D, Somjen G J, Harell A, Mechanic G L, Binderman I. 1982. Partial characterization of specific high affinity binding macromolecule for 24R,25-dihydroxyvitamin D_3 in differentiating skeletal mesenchyme. Biochem Biophys Res Commun, 1982, 106: 644-651.
176.Staal A, Geertsma Kliinekoort W M. Regulation of os-teocalein prodution and bone resorption by 1,25 dihydrox-yvitamin D_3 in mouse long bone interaction with the bone-derived growth factors TGF-beta and IGF-1. J Bone Miner Res, 1998, 13: 36-43.
177.Stewart C E, Rotwein P. Growth different and survial: multiple physiological function for insulin-like factors. Physiol Rev, 1996, 76: 1005-1026.
178.Suh S J, Yun W S, Kim K S, Jin U H, Kim J K, Kim M S, Kwon D Y, Kim C H. Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic
MC3T3-E1 cells. J Ethnopharmacology, 2007, 109: 480-485.
179.Suliman I A, El-Bakri N K, Adem A, Mustafa A, Lindgren J U. The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur. J Orthop Res, 2001, 19: 1008-1012.
180.Sykes A R, Field A C. Effects of dietary deficiencies of energy, protein, and calcium on pregnant ewes. 1. Body composition and mineral content of ewes. J Agric Sci, 1972,78:109.
181 .Thornberry N A, Lazebnik Y. Caspases: enemies within. Science, 1998, 281: 1312-1316.
182.Tillman A D, Brethour J R. The effect of corn oil upon the metabolism of calcium and phosphorus by sheep. J Anim Sci, 1958, 17: 782-786.
183.Tomas F M, Moir R J, Somers M. Phosphorus turnover in sheep. Aust J Agric Res, 1967,18:635-645.
184.Tomas F M. Phosphorus homeostasis in sheep. If. Influence of diet on the pathway of excretion of phosphorus. Aust JAgric Res, 1974, 25: 485-493.
185.Tong A L, Chen L L, Ding G Z. Reseach Advancement of the mechanism of bone formation regulated by osteoblasts. Chin J Osteoporos, 1999, 3: 60-64.
186.Trippel S B. Potential role of insulin-like growth factors in fracture healing. Clin Orthop, 1998, 355 (Suppl): S301-313.
187.Tumber A, Meikle M C, Hill P A. Autocrine signals promote osteoblasts survial in culture. Endocrine J, 2000, 167: 383-390.
188.Umayahara Y, Billiard J, Ji C, Centrella M, McCarthy T L, Rotwein P. CCAAT/enhancer-binding protein delia is a critical regulatior of insulin-like growth factor-I gene transcription of osteoblasts. J Biol Chem, 1999, 274: 10609-10617.
189.Visek W J, Monroe R A, Swanson E W, Comar C L. Calcium metabolism in dairy cows as studied with Ca45. J Dairy Sci, 1953, 36: 373-383.
190.Wang L, Ma W, Markovich R, Chen J W, Wang P H. Regulation of cardiomyocyte apoptotic signaling by insulin-like growth factor I. Circ Res, 1998, 83:516-522.
191. Ward G, Harbers L H, Blaha J J. Calcium-containing crystals in alfalfa: Their fate in cattle. J Dairy Sci, 1979, 62: 715-722.
192.Ward G, Dobson R C, Dunham J R. Influences of calcium and phosphorus intakes, vitamin D supplementation, and lactation on calcium and phosphorus balances. J Dairy Sci, 1971, 55:768-776.
193.Wasserman R H, Taylor A N. Gastrointestinal absorption of calcium and phosphorus, in Handbook of physiology. In: Aubach G D ed., Sect. 7: Endocrinology. Vol. VII, Parathyroid gland. Washington DC: Am Physiol Soc, 1976. 137-155.
194.Wasserman R, Fullmer C S, Shimura F. Calcium absorption and the moleculareffects of vitamin D_3 in vitamin D. In: Kumar R ed., Basic and clinical aspects. Boston, MA: Martinus Nijhoff Publ, 1984. 233-258.
195.Wergedal J E, Baylink D J. Characterization of cells isolated and cultured from human bone. Pro Soc Exp Bio Med, 1984, 176: 60-69.
196.Yanpaisan W, King N J C, Doran P M. Flow cytometry of plant cells with applications in large-scale bioprocessings. Biotechnol Adv, 1999, 17: 3-27.
197.Yeh L C C, Adamo M L, Olson M S, Lee J C. Osteogenic protein-1 and insulin-like growth factor-1 synergistically stimulate rat osteoblastic cell differentiation and proliferation.Endocrinology,1997,138:4181-4190.
198.Yeh L C C,Lee J C,Co-transfection with the osteogenic protein(OP)-1 gene and the insulin-like growth factor(IGF)-1 gene enhanced osteoblastic cell differentiation.BBA-Molecular Cell Research,2006,1763:57-63.
199.Zhang K Q,Chen J W,Wang M L.The expression of insulin-like growth factor-1mRNA and polypeptide in rat osteoblasts with exposure to parathyroid hormone.Chinese Med J,2003,116:1916-1922.
200.Zhang X,Sobue T,Hurley M M.FGF-2 increases colony formation,PTH receptor,and IGF-I mRNA in mouse marrow stromal cells.Biochem Biophys Res Commun,2002,290:526-531.
2.姜华,王稚英,姚琦,张立海.缺氧对成骨细胞增殖及凋亡的影响.口腔颌面修复学杂志,2005,5:81-83.
3.刘彬,丁卫,谷静丽,葛韵琴,杜国光.EGF及IGF-I对UMR106细胞增殖及β-微管蛋白表达的影响.生物化学杂志,1995,11:406-41.
4.刘根桃,陈伟华,郑元林等.胰岛素养生长-1的放射免疫测定方法的建立.南京农业大学学报,1999,22:63-66.
5.刘真喜,傅焕,赵彤.IGF-1与细胞凋亡的研究进展.医学综述,2001,10:579-580.
6.刘忠厚主编.骨质疏松学.北京:科学出版社,1998,91-93.
7.石义刚,陶天遵,陶树清,刘枫晨,徐强,王立春,吉光荣,吴丽萍.rhIGF-1对成骨细胞增殖、分化及骨保护素、骨保护素配体基因mRNA表达的影响.中国骨质疏松杂志,2003,9:31-34.
8.斯佩克特D L.细胞实验指南.黄培堂译.北京:科学出版社,2001,93-98.
9.宋爱梅,束蓉.体外培养骨髓间充质干细胞向成骨细胞分化的影响因素研究.牙体牙髓牙周病学杂志,2005,15:55.
10.孙玉芳.奶牛血清碱性磷酸酶及钙磷含量的测定与分析.中国奶牛,1996,6:12.
11.唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量的测定.中国兽医科技,2002,32:26-28.
12.唐孝明,裴福兴,沈彬,刘仲前,张耀明,庞健.雌激素对血清饥饿诱导成骨细胞凋亡的影响.中国康复理论与实践,2006,12:123-125.
13.王九峰,金久善,夏兆飞,朱要宏.骨钙素在乳牛骨软病研究上的重要性.畜牧兽医学报,1999,30:513-518.
14.王卫华,于世凤.成骨细胞体外培养方法研究进展.国外医学口腔医学分册,1996,23:287-291.
15.王智兴,李群,张玥,朱亚萍.成骨生长肽对成骨细胞样细胞的分化和成骨作用.上海第二医科大学学报,2000,20:227-229.
16.徐成丽,鄢盛恺,祖淑玉,沈瑛,翟凤英,韩少梅,张李伟,朱广瑾.2342例北京地区儿童血清钙、无机磷水平检测分析.中国医学科学院学报,2004,26:455-459.
17.徐萍,张克勤,刘超,刘翠萍,唐伟.重组人胰岛素样生长因子I对大鼠成骨细胞增殖、凋亡及I型胶原蛋白合成的影响.中国骨质疏松杂志,2006,12:17-21.
18.杨景山.医学细胞化学与细胞生物技术.北京:北京医科大学,中国协和医院大学联合出版社,1990,42.
19.余增丽,韩萍,李文杰.染料木黄酮对人成骨细胞凋亡的影响.营养学报,2004,26:288-291.
20.曾晓峰,赵建宁.骨保护素及其配体对破骨细胞功能的调控作用.中国矫形外科杂志,2004,12:463-465.
21.翟中和,王喜忠,丁明孝.细胞生物学.北京:高等教育出版社,2000,357-360.
22.张吉富.测骨矿物质含量诊断奶牛钙磷代谢障碍.中国兽医科技,1993,23:33-34.
23.张明,金惠铭,曹翔,刘清行,钱睿哲,张国平.低浓度H_2O_2对肺微血管内皮细胞的迟发效应-凋亡.中国病理生理杂志,1999,15:28.
24.张兴凯,杨庆铭,邓廉夫,朱雅萍.成人成骨细胞体外培养.中华外科杂志,2000,38:51-53.
25.张玉静.分子遗传学.北京:科学出版社,2000,27.
26.郑晓辉,方秀斌.骨钙素的基础与应用研究进展.解剖科学进展,1999,4:327-329.
27.周洪涛,李风洲,宁自利.乳牛血清钙磷乘积与骨密度的关系.黑龙江畜牧兽医,1996,1:6-7.
28.朱新民,王加启.奶牛钙磷代谢的常见问题及其机理.中国畜牧兽医,2005,13:23-25.
29.左爱仁,范青生.细胞凋亡及其机制的研究.生物学教学,2003,6(28):7-9.
30. Aarskog D, Aksnes L. Acute response of plasma 1,25-dihydroxyvitamin D to parathyroid hormone. Lancet, 1980, 16: 362-363.
31. Calo L, Castrigano R, Davis P A. Role of insulin-like growth factor-I in primary osteoporosis: a correlative study. J Endocrionl invest, 2000,23: 223-237.
32. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, Yoshiki S, Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D_3. Proc Natl Acad Sci, 1981, 78: 4990-4994.
33. Alborzi A, Mac K, Glackin CA, Murray S S, Zernik, JH. Endochondral and intramembranous fetal bone development: osteoblastic cell proliferation and expression of alkaline phosphatese, M-twist, and histone H4. J Craniofac Genet Dev Biol, 1996, 16:94-106.
34. Atkins G J, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdoliou A, Harrison K, Findlay D M, Zannettino A C. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res, 2003, 18: 1008-1098.
35. Barton B A, Hodnett D W, Jorgensen N A, DeLuca H F. 24,25-Dihydroxyvitamin D_3 administration increases incidence of parturient paresis. J Dairy Sci, 1984, 67: 1236-1239.
36. Barton B, Jorgensen A N A, Horst R L, DeLuca H F. Influence of dietary phosphorus level on the concentration of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, calcium and phosphorus in plasma of aged dairy cows. J Dairy Sci, 1978, 61: 145 (Abstract).
37. Bautista C M, Mohan S, Baylink D J. Insulin-like growth factor- I and II arepresent in the skeletal tissues of ten vertebrates. Metabolism, 1990, 39: 96-100.
38. Baxter R C. Molecular aspects of insulin-like growth factor binding proteins. In: LeRoith D ed., Advances in Molecular and Cellular Endocrinology. Greenwich: JAI Press, 1997. Vol 1,123-159. .
39. Baxter R C. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab, 2000, 278: E967-76.
40. Bellows C G, Aubin J E, Heersche J N M, Antosz M E. Mineralised bone nodules formed in vitro from enzymatically released rat calvaria cell populations. Calcif Tissue Int, 1986,38:143-437.
41. Bing 0 H L. Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure over-load. J Mol Cell Cardiol, 1994, 26: 943-948.
42. Bordier P, Rasmussen H, Marie P, Miravet L, Gueris J, Ryckwaert A. Vitamin D metabolite and bone mobilization in man. J Clin Endocrinol Metab, 1978, 46: 284-294.
43. Bourrin S, Ammann P, Bonjour J P, Rizzoli R. Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats. Endocrinology, 2000, 141:3149-3155.
44. Braithwaite G D. Calcium and phosphorus metabolism in ruminants with special reference to parturient paresis. J Dairy Res, 1976,43: 501-520.
45. Braithwaite G D. Calcium and phosphorus requirements of the ewe during pregnancy and lactation. 2. Phosphorus. Br J Nutr, 1983, 50: 723-736.
46. Broadus A E, Horst R L, Lang R, Littledike E T, Rasmussen H. The importance of circulating 1,25-dihydroxyvitamin D in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. N Engl J Med, 1980, 302: 421-426.
47. Campbell P I, Breedlove D K, Kempson S A. Insulin-like growth factor I stimulates sodium-phosphate cotransport in the rat oeteoblastic cell line UMR-106-01. Am J Physiol, 1992,262: E389-93.
48. Canalis E, McCarthy T, Centrella M. Isolation of growth factors from adult bovine bone. Calcif Tissue Int, 1988,143, 346-351.
49. Canterbury J M, Lerman S, Claflin A J, Henry H, Norman A, Reiss E. Inhibition of parathyroid hormone secretion by 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol in the dog. J Clin Invest, 1978, 61: 1375-1383.
50. Care A D, Barlet J P, Abdel-Hafeez H M. Calcium and phosphate homeostasis in ruminants and its relationship to the actiology and prevention of parturient paresis. In: Ruckebusch Y, Thivend D ed., Digestive physiology and metabolism in ruminants. Westport CT: AVI Publ Co., Inc., 1980. 429-445.
51. Celiker R, Arslan S. Comparison of serum insulin-like growth factor-1 and growth hormone levels in osteoporotic and non-osteoporotic postmenopausal women. Rheumatol Int, 2000, 19: 205-208.
52. Chang Y L, Stanford C M, Keller J C. Calcium and phosphate supplementation promotes bone cell mineralisation: implications for hydroxyapatite (HA)-enhanced bone formation. J Biomed Mater Res, 2000, 52: 270-278.
53. Clark R. A study of the water-soluble phosphate concentration of the ruminal contents in normal and phosphorus deficient animals. Onderstepoort J Vet Res, 1953.26:137.
54. Cohen R D H. Phosphorus in rangeland ruminant nutrition: A review. Livestock Prod Sci, 1980,7:25-37.
55. Collignon H, Davicco M J, Barlet J P. Isolation of cells from ovine fetal long bone and characterization of their osteoblastic activities during in vitro mineralization. Arc of Physics and Biochemistry, 1997, 105: 158-166.
56. Colovos N F, Keener H A, Davis H A. Effect of pulverized limestone and calcium phosphate on the nutritive value of dairy cattle feed. J Dairy Sci, 1958, 41: 676.
57. Curtis C R, Erb H N, Smiffen G J, Smith R D, Powers P A, Smith M C, White M E, Hillman R B, Pearson E J. Association of parturient hypocalcemia with periparturient disorders in Holstein cows. J Am Vet Med Assoc, 1983, 183: 559-561.
58. Davicco M J, Remond B, Jabet S, Barlet J P. Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period. Reprod Nutr Dev, 1992,32,313-319.
59. Dclany A M, Rydzicl S, Canalis E. Autocrine down-regulation of collagenase-3 in rat bone cell culture by insulin-like growth factor. Endocrinology, 1996, 137: 4665-4670.
60. Delany A M, Pash J M. Canalis E. Cellular and clinical per-spectives on skeletal insulin-like growth factor I. J Cell Biochem, 1994, 55: 328-333.
61. DeLuca H F. Recent advances in the metabolism of vitamin D. Ann Rev Physiol, 1981,43: 199-209.
62. Doleze I J. Flow cytometetry analysis of nuclear DNA content in higher plants. Phytochem Anal, 1991,2: 143-154.
63. Dulak N, Temin H. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication stimulating activity for embryo fibroblasts. J Cell Physiol, 1973,81:153-160.
64. Ernst M, Rodan G A. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone(GH): positive correlation with the presence of the GH-induced IGF- binding protein BP-3. Endocrinology 1990,127:807-814.
65. Ernst M, Rodan G A. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3. Endocrinology, 1990, 127: 807-814.
66. Fiedler J, Brill C, Blum W F, Brenner R E. IGF-1 and IGF-2 stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Bio Biophysical Res Communications, 2006, 345: 1177-1183.
67. Froesch E R, Burgi H, Ramseier E B, Bally P, Labhart A. Antibody suppressible and non-suppressible insulin-like activities in human serum and their physiological significance. J Clin Invest, 1963. 42:1816-1834.
68. Galbraith D W, Harkins K R, Maddox J M. Rapid cycle in intact plant tissue. Science, 1983,220:1049-1051.
69. Gallagher J C, Riggs B L, DeLuca H F. Effects of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab, 1980,51: 1359-1364.
70. Gast D R, Horst R L, Jorgensen N A, DeLuca H F. Potential use of 1,25-dihydroxyvitamin D_3 or prevention of parturient paresis. J Dairy Sci, 1979, 62: 1009-1013.
71. Gluckman P D, Douglas R G, Ambler G R, Breier B H, Hodgkinson S C, Koea J B, Shaw J H. The endocrine role of insulin-like growth factor I. Acta Paediatric Scand, 1991, 372(Suppl): 97-105.
72. Goad D L, Rubin J, Wang H, Tashjian A H Jr, Patterson C. Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I. Endocrinology, 1996, 137:2262-2268.
73. Goff J P. Calcium homeotasis challenged during lactation. Feedstuff's, 1989, 61: 29.
74. Goings R L, Jacobson N L, Beitz D C, Littledike E T, Wiggers K D. Prevention of parturient paresis by prepartum, calcium deficient diet. J Dairy Sci, 1974, 57: 1184-1188.
75. Grace N D, Ulyatt M J, MacRae J C. Quantitative digestion of fresh herbage by sheep. 3. Movement of Mg, Ca, P, K, and Na in digestive tract. J Agric Sci, 1974, 82:321.
76. Grace N D. Phosphorus kinetics in sheep. Br J Nutr, 1981,45:367.
77. Grant A B. Carotene: A rachitogenic factor in green feeds. Nature, 1953, 172: 627.
78. Gray R W. Control of plasma 1,25-(OH)_2 vitamin D concentrations by calcium and phosphorus in the rat: Effects of hypophysectomy. Calcif Tiss Int, 1981, 33: 485-488.
79. Green J, Goldberg R, Maor G PTH ameliorates acidosis-induced adverse effects in skeletal growth centers: the PTH-IGF-I axis. Kidney Int, 2003,63: 487-500.
80. Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab, 2002, 87: 2883-2891.
81. Hague A, Hicks D J, Bracey T S. Cell-cell contact amd specific cytokines inhibit apoptosis of colonic epithelial cells: growth factors protect against c-myc-independent apoptosis. BrJCancer, 1997, 75: 960-968.
82. Hanai Y, Tokuda H, Ishisaki A, Matsushima-Nishiwaki R, Nakamura N, Yoshida M, Takai S, Ohta T, Kozawa O. Involvement of p44/p42 MAP kinase in insulin-like growth factor-1 induced alkaline phosphatase activity in osteoblast-like-MC3T3-El cells. Mol Cell Endo, 2006,251: 42-48.
83. Hansard S L, Crowder H M, Lyke W A. The biological availability of calcium in feeds for cattle. J Anita Sci, 1957, 16:437-443.
84. Hayden J M, Mohan S. Baylink D J. The insulin-like growth-factor system and the coupling of formation to resorption. Bone, 1995, 17(2 Supply): 93S-98S.
85. He J, Rosen C J, Adams D J, Kream B E. Postnatal growth and bone mass in mice with IGF-1 haploinsufficiency. Bone, 2006, 38: 826-835.
86. Herault O, Domenech J, Georget M T. All-trans retinoic acid prevents apoptosis of human marrow CD~(34+) cells deprived of haematopoietic growth factors. Br J Haematology, 2002, 118: 289-295.
87. Hibbs J W, Pounden W D. Studies on milk fever in dairy cows. IV. Prevention by shorttime prepartum feeding of massive doses of vitamin D. J Dairy Sci, 1955, 38: 65-72.
88. Hibbs, J W, Conrad H R. The relation of calcium and phosphorus intake and digestion and the effects of vitamin D feeding on the utilization of calcium and phosphorus by lactating dairy cows. Ohio Agric Res Dev Ctr Res Bull, 1983, 150: 1-26.
89. Hill P A, lumber A, Meikle MC. Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology, 1997, 138: 3849-3858.
90. Hoffsis G F, Capen C C, Norman A W. The use of 1,25-dihydroxycholecalciferol in the prevention of parturient hypocalcemia in dairy cows. Bovine Pract, 1979, 13: 88.
91. Horst R L, Jorgensen N A, DeLuca H F. Plasma 1,25-dihydroxyvitamin D and parathyroid hormone levels in paretic dairy cows. Am J Physiol Gastrointest Liver Physiol, 1979a, 236: E634 (Abstract).
92. Horst R L, Jorgensen N A. Elevated plasma cortisol during induced and spontaneous hypocalcemia. J Dairy Sci, 1982, 65: 2332-2337.
93. Horst R L, Littledike E T. Comparison of plasma concentrations of vitamin D and its metabolite in young and aged domestic animals. Comp Biochem Physiol B, 1982, 73: 485-489.
94. Horst R L, Shepard R M, Jorgensen N A, DeLuca H F. The determination of vitamin D metabolites in a single plasma sample. Changes during parturition in dairy cows. Arch Biochem Biophys, 1979b, 192: 512-523.
95. Horst R W, DeLuca H F, Jorgenson N. Effect of age on calcium absorption and accumulation of 1,25-dihydroxyvitamin D_3 in intestinal mucosa of rats. Metab Bone Dis Rel Res, 1978,1: 29-34.
96. Hove K, Horst R L, Littledike E T, Beitz D C. Infusions of parathyroid hormone in ruminants: Hypercalcemia and reduced plasma 1,25-dihydroxyvitamin D concentrations. Endocrinology, 1984,114: 897-903.
97. Hsu Y L, Chang J K, Tsai C H, Chien T T, Kuo P L. Myricetin induces human osteoblast differentiation through bone morphogenetic protein-2/p38 mitogen-activated protein kinase pathway. Biochemical Pharmacology, 2007, 73: 504-514.
98. Iranmanesh A, Veldhuis J D. Clinical pathophysiology of the somatotropic (GH) axis in adults. Endocrinol Metab Clin North Am, 1992,21: 783-816.
99. Ishizuya T, Yokose S, Hori M. Parathyroid hormone exerts disparate effects on osteoblast differentiation on exposure time in rat osteoblastic cells. J Clin Inv, 1997,99:2961-2970.
100.Jasen M, Schaik F M A, Ricker A T, Bullock B, Woods D E, Gabbay K H, Nussbaum A L, Sussenbach J S, Van-Den-Brande J L. Sequence of cDNA encoding human insulin-like growth factor- I precursor. Nature, 1983, 306: 609-611.
101.Jia TL, Wang H Z, Xie L P, Wang X Y, Zhang R Q. Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production. Biochem Pharm, 2003,65: 709-715.
102.Jilka R L, Weinstein R S, Bellido T, Parfitt A M, Manolagas S C. Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res, 1998, 13: 793-802.
103.Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology, 1996, 137: 2187-2190.
104.Johansson A G, Lindh E, Ljunghall S. Insulin-like growth factor I stimulates bone turn over in osteoporosis. Lancet, 1992, 339: 1619.
105.Jonsson K B, Ljunghall S, Karlstrom O, Johansson A G, Mallmin H, Ljunggren O. Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts. Biosci Rep, 1993, 13: 297-302.
106.Jorgensen N A. Combating milk fever. J Dairy Sci, 1974, 57: 933-944.
107.Key L, Carnes D, Cole S, Holtrop M, Bar-Shavit Z, Shapiro F, Arceci R, Steinberg J, Gundberg C, Kahn A, Teitelbaum S, Anast C. Treatment of congenital osteopetrosis with high-dose calcitriol. N Engl J Med, 1984, 310: 409-415.
108.Kichura T S, Horst R L, Beitz D C, Littledike E T. Relationships between prepartal dietary calcium and phosphorus, vitamin D metabolism and parturient paresis in dairy cows.J Nutr,1982,112:480-487.
109.Kimura T,Majima Y,Guo Y,Yoshida T.The effect of growth factors on the proliferation and differentiation of human nasal gland cells.Arch Otolaryngol Head Neck Surg,2002,128:578-582.
110.Kong Y Y,Yoshida H,Sarosi I,Tan H L,Timms E,Cappareli C,Morony S,Oliveira-dos-Santos A J,Van G,Itie A,Khoo W,Wakenhan A,Dunstan C R,Lacey D L,Mak T W,Boyle W J,Penninger J M.OPGL is a key regulator of osteoclastogensi,lymphocyte development and lymph-node organogenesis.Nature,1999,397:315-323.
111.Kooijman R.Regulation of apoptosis by insulin-like growth factor(IGF)-I.Cytokine Growth Factor Rev,2006,17:305-323.
112.Kovacina K S,Steele-Perkins G,Roth R A.A role for the insulin-like growth factor Ⅱ/mannose-6-phosphate receptor in the insulin-induced inhibition of protein catabolism.Mol Endocrinol,1989,3:901-906.
113.Krook L,Lutwak L,McEntee K,Herrikson P A,Braun K,Roberts S.Nutritional hypercalcitonism in bulls.Cornell Vet,1971,61:625-639.
114.Kudo Y,Iwahita M,Takeda Y.Evidece for modu-lation of osteocalcin containing gamma-carboxyglutamic acid residues synthesis by insulin-like growth faxtor-I and vitamin K_2 in human osteosarcoma cell line MG-63.Eur J Endocrinol,1998,138:443-448.
115.Kudo Y,Iwashita M,Iguchi T,Takeda Y.The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells.Pflugers Arch,1996,432:419-426.
116.Kveiborg M,Flyvbjerg A,Eriksen E F,Kassem M.1,25-Dihydroxyvitamin D_3stimulates the production of insulin-like growth factor-binding proteins-2,-3 and -4 in human bone marrow stromal cells.Eur J Endocrinol,2001a,144:549-557.
117.Kveiborg M,Flyvbjerg A,Edksen E F,Kassem M.Transforming growth factor-β1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors.J Endocrinol,2001b,169:549-561.
118.Lacey D L,Tan H L,Lu J,Kaufman S,Van G,Qiu W,Rattan A,Scully S,Fletcher F,Juan T,Kelley M,Burgess T L,Boyle W J,Polverino A J. osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Amer J Pathology, 2000, 157: 435-448.
119.Langdahl B L, Kassem M, Moller M K, Eriksen E F. The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone. Eur J Clin Invest, 1998, 28: 176-183.
120.Lazowski D A, Fraher L J, Hodsman A, Steer B, Modrowski D, Han VK. Regional variation of insulin growth factor-I gene expression in mature rat bone and cartilage. Bone, 1994, 15: 563-576.
121.LeBlanc A C. Natural cellular inhibitors of caspases. Prog Neuropsychopharmacol Biol Psychiatry, 2003, 27: 215-229.
122.Leibholtz, J. Flow of calcium and phosphorus in digestive tract of sheep. Aust J Agric Res, 1974,25:147-154.
123.Li D W, Qin L L.. Effects of genistein on proliferation, differentiation, content of matrix calcium and mineralisation of cultured osteoblasts in vitro. Chin J Osteoporo, 2002, 8: 307-311.
124.Li Z X, Liu H M, Zhao D S. Diagnose and treatment of osteomalacia of dairy cow. Chin J Vet Med, 1996, 22: 27.
125.Lindsay R, Hart D M, Aitken J M,. Long-term prevention of postmenopausal osteoporosis by estrogen; Evidence for an increased bone mass after delayed onset of estrogentreatment. Lancet, 1986,1: 1038-1041.
126.Littledike E T, Horst R L. Inappropriate plasma 1,25-(OH)_2D response to parturient hypocalcemia in cows treated with vitamin D3, 1,25-(OH)_2D_3 or 1,25,26-(OH)_3D_3 prepartum.In: Norman A W, Schaefer K, Herrath D V, Grigoleit H G, eds., Vitamin D, chemical, biochemical and clinical endocrinology of metabolism. New York, NY: Walter de Gruyter, 1982. 475.
127.Lomba F, Chauvaux G, Teller E, Lengele R, Bienfet V. Calcium digestibility in cows as influenced by excess of alkaline ions over stable acid ions in their diets. Br J Nutr, 1978,39:425-429.
128.Louitit J F, Nisbet N W. The origin of osteoclasts, Immunobiology, 1982, 161: 193-203.
129.Ma Z J, Misawa H, Yamaguchi M. Stimulatory effect of zinc on insulin-like growth factor-I and transforming growth factor-beta production with bone growth of newborn rats. Int J MolMed, 2001, 8: 623-628.
130.Maccario M, Grottoli S, Camanni F. IGF-I levels in different conditions of low somatotrope secretion in adulthood:obesity in comparison with GH deficiency. Minerva Endocrinol, 1999,24: 57-61.
131.Mackie E J. Osteoblasts: novel roles in orchestration of skeletal architecture. International Joutnal of Biochemistry and Cell Biology, 2003, 35: 1301-1305.
132.Malpe R. Baylink D J. Linkhart T A, et al. Insulin growth factor(IGF)-I, -II, IGF binding proteins(IGFBP)-3f -4 and -5 levels in the conditioned media of normal human bone cells are skeletal site-dependent. J Bone Miner Res, 1997, 12: 423-30.
133.Malyszko J S, Wolczynski S, Mysliwiec M. Osteoprotegerin and its correlations with new markers of bone formation and bone resorption in kidney transplant recipients. Trans Proceedings, 2003, 35: 2227-2229.
134.Marie P. Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-beta. Rev Rhum Engl Ed, 1997,64: 44-53.
135.Marquardt J P, Holick M F, Horst R L, Jorgensen N A, DeLuca H F. Efficiency of 1α-hydroxyvitamin D_3 on prevention of parturient paresis. J Dairy Sci, 1974, 57: 606.
136.Marquardt J P, Horst R L, Jorgensen N A. Effect of parity on dry matter intake at parturition in dairy cattle. J Dairy Sci, 1977,60: 929-934.
137.Melissa K. Calcium metabolism and metabolic bone disease. Herp Care Collection, April, 2007. http://www.anapsid.org/mbd2.html 543(accessed 01.04.2007).
138.Middleton J, Arnott N, Walsh S. Osteoclasts in adult human osteophyte tissue express the mRNAs for IGF-1 and II and the type-Ⅰ IGF receptons. Bone, 1995, 16:287-293.
139.Mitsiades C S, Mitsiades N, Poulaki V, Schlossman R, Akiyama M, Chauhan D. Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications, Oncogene, 2002,21: 5673-5683.
140.Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, Tanaka K, Kumegawa M. Insulin-like growth factor-I supports formation and activation of osteoclasts. Endoceinology, 1992, 131:1075-1080.
141.Moe P W. Effects of level of intake on the utilization of diets by dairy cows. (Ph D thesis). Ithaca, NY: Cornetl Univ, 1965.
142.Murgo A J, Fried J, Burchenal D, Vale K L, Strife A, Woodcock T, Young C W, Clarkson B D. Effects of thymidine and thymidine plus 5-fluorouracil on the growth kinetics of a human lymphiod cell line. Cancer Res, 1980,40: 1543-1549.
143.Napoli J L, Sommerfeldt J L, Pramanik B C, Gardner R, Sherry A D, Partridge J J, Uskokovic M R, Horst R L. 19-Nor-10-ketovitamin D derivatives: Unique metabolites of vitamin D3, vitamin D2, and 25-hydroxyvitamin D3. Biochemistry, 1983. 22: 3636-3640.
144.Nasu M, Sugimoto T, Kaji H, Chihara K. Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5. Journal of Endocrinology, 2000, 167: 305-313.
145.National Research Council. Nutrient requirements of dairy cattle. 6th ed. Washington DC, 1978.
146.Norman A W. 1,25-Dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D_3: Key components of the vitamin D endocrine system. Contrib Nephrol, 1980, 18: 1-11.
147.OjO S A, Leipald H W, Cho D Y, Guffy M M. Osteopetrosis in two Hereford calves. J Am Vet Med Assoc, 1975, 166: 781-783.
148.01ney R C. Regulation of bone mass by growth hormone. Med Pediatr Oncol, 2003,41:228-234.
149.Olson W G, Jorgensen N A, Schultz L H, DeLuca H F. 1973. 25-Hydroxycholecalciferol (25-OHD_3) I. Treatment for parturient paresis. J Dairy Sci, 1973,56:885-888.
150.Ortiz C O, Chen B K, Bale LK, Overgaard M T, Oxvig C, Conover C A. Transforming growth factorbeta regulation of the insulin-like growth factor binding protein-4 protease system incultured human osteoblasts. J Bone Miner Res, 2003, 18: 1066-1072.
151.Palumbo C, Palazzini S, Marotti G. Morphological study of intercellular junctions during osteocyte differentiation. Bone, 1990,11: 401-406.
152.Panagakos F S. Insulin-like growth factors-I and-II stimulate chemotaxis of osteoblasts isolated from fetal rat calvaria. Biochimie, 1993, 75: 991-994.
153.Patel S, Lyons A R, Hosking D J. Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. Drugs, 1996,46: 594-617.
154.Pepene C E, Kasperk C H, Pfeilschifter J. Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro. Bone, 2001,29:540-546.
155.Peters M A, Lau E P, Snitman D L, Van W J, Underwood L E, Russel W E, Svoboda M E. Expression of a biologically active analogue of somatomedin-C/insulin-like growth factor-1. Gene, 1985, 35: 83-89.
156.Peterson W J. A method to assess the proliferating activity of small numbers of murine peripheral blood mononuclear cells. J Immunol Methods, 1987, 96: 171-176.
157.Poulaki V, Mitsiades C S, Kotoula V, Tseleni-Balafouta S, Ashkenazi A, Koutras D A. Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells, Am J Pathol, 2002, 161: 643-654.
158.Power R A, Iwaniec U T, Wronski T J. Changes in gene expression associated with the bone anabolic effects of basic fibroblast growth factor in aged ovariectomized rats. Bone, 2002, 31: 143-148.
159.Raile K, Hoflich A, Kessker U. Human osteosarcoma (U-2 OS) cells express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth- II /mannose-6 phosphate (IGF- II /M6P) receptors and synthesize IGF-I: Autocrine growth stimulation by IGF- II via the IGF-I receptor. J Cell Physiol, 1994, 159:531-541.
160.Ramberg C F, Johnson E K, Fargo R D, Kronfeld D S. Calcium homeostasis in cows with special reference to parturient hypocalcemia. Am J Physiol Regul Integr Comp Physiol, 1984,246: R698- R704.
161.Ramberg C F, Kronfeld D S, Wilson G D A. Regulation of calcium metabolism in cattle during growth, lactation, and change in diet. In: McDonald I W, Warner A C I eds., Digestion and metabolism in the ruminant. Armidale Aust: Univ New Engl Publ Unit, 1975.231-242.
162.Rinderknecht E, Humbel R E. Primary structure of human insulin-like growth factor- II. FEBS Lett, 1978a, 89: 283-286.
163.Rinderknecht E, Humbel R E. The amino acid sequence of human insulin-like factor- I and its structural homology with proinsulin. J Biol Chem, 1978b, 253: 2769-2776.
164.Robey P G, Termine J D. Human bone cells in vitro. Calcif Tissue Int, 1985, 37: 453-460.
165.Roth J A, Kaeberle M L. Effect of glucocorticoids on the bovine immune system. J Am Vet Med Assoc, 1982, 180: 894-901.
166.Rowland G N, Capen C C, Young D M, Black H E. Micrographic evaluation of bone from cows with experimental hypervitaminosis D, diet induced hypocalcemia, and naturally occurring parturient paresis. Calcif Tiss Res, 1972, 9: 179-193.
167.Rydziel S, Delany A M, Canalis E. Insulin-like growth factor I inhibits the transcription of collagenase 3 in osteoblast culture. J Cell Biochem, 1997, 67: 176-83.
168.Sachs M, Bar A, Cohen R, Mazur V, Mayer E, Hurwitz S. Use of 1α-hydroxycholecalciferol in prevention of bovine parturient paresis. Am J Vet Res, 1977, 38: 2039.
169.Salmon W D, Daughaday W H. A hormonally controlled serum factor which stimulates sulphate incorporation by cartilage in vivo. J Lab Clin Med, 1957, 49: 825-836.
170.Sara V R, Hall K. Insulin-like growth factors and their binding proteins. Physiol Reviews, 1990,70:591-614.
171.Scheven B A A, Hamilton N J, Fakkeldij T M V, Duursma S A. Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells. Growth Regul, 1991, 1: 160-167.
172.Seynaeve M, Janssens G, Hesta M, Van Nevel C, De Wilde R O. Effects of dietary Ca/P ratio, P level and microbial phytase supplementation on nutrient digestibilities in growing pigs: breakdown of phytic acid, partition of P and phytase activity along the intestinal tract. J Anim Physiol Anim Nutr, 2000, 83, 193-204.
173.Smith P N, Padilla M, Wasserman RH, Kallfelz F A. Calcium and 24,25-dihydroxyvitamin D: Inverse relation in cows with parturient paresis. Calcif Tiss Int, 1982,34: 564-566.
174.Smith V R, Merrill W G Parturient paresis. VII. A study of the leukocytes of cows with parturient paresis. J Dairy Sci, 1954, 37: 967-975.
175.Somjen D, Somjen G J, Harell A, Mechanic G L, Binderman I. 1982. Partial characterization of specific high affinity binding macromolecule for 24R,25-dihydroxyvitamin D_3 in differentiating skeletal mesenchyme. Biochem Biophys Res Commun, 1982, 106: 644-651.
176.Staal A, Geertsma Kliinekoort W M. Regulation of os-teocalein prodution and bone resorption by 1,25 dihydrox-yvitamin D_3 in mouse long bone interaction with the bone-derived growth factors TGF-beta and IGF-1. J Bone Miner Res, 1998, 13: 36-43.
177.Stewart C E, Rotwein P. Growth different and survial: multiple physiological function for insulin-like factors. Physiol Rev, 1996, 76: 1005-1026.
178.Suh S J, Yun W S, Kim K S, Jin U H, Kim J K, Kim M S, Kwon D Y, Kim C H. Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic
MC3T3-E1 cells. J Ethnopharmacology, 2007, 109: 480-485.
179.Suliman I A, El-Bakri N K, Adem A, Mustafa A, Lindgren J U. The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur. J Orthop Res, 2001, 19: 1008-1012.
180.Sykes A R, Field A C. Effects of dietary deficiencies of energy, protein, and calcium on pregnant ewes. 1. Body composition and mineral content of ewes. J Agric Sci, 1972,78:109.
181 .Thornberry N A, Lazebnik Y. Caspases: enemies within. Science, 1998, 281: 1312-1316.
182.Tillman A D, Brethour J R. The effect of corn oil upon the metabolism of calcium and phosphorus by sheep. J Anim Sci, 1958, 17: 782-786.
183.Tomas F M, Moir R J, Somers M. Phosphorus turnover in sheep. Aust J Agric Res, 1967,18:635-645.
184.Tomas F M. Phosphorus homeostasis in sheep. If. Influence of diet on the pathway of excretion of phosphorus. Aust JAgric Res, 1974, 25: 485-493.
185.Tong A L, Chen L L, Ding G Z. Reseach Advancement of the mechanism of bone formation regulated by osteoblasts. Chin J Osteoporos, 1999, 3: 60-64.
186.Trippel S B. Potential role of insulin-like growth factors in fracture healing. Clin Orthop, 1998, 355 (Suppl): S301-313.
187.Tumber A, Meikle M C, Hill P A. Autocrine signals promote osteoblasts survial in culture. Endocrine J, 2000, 167: 383-390.
188.Umayahara Y, Billiard J, Ji C, Centrella M, McCarthy T L, Rotwein P. CCAAT/enhancer-binding protein delia is a critical regulatior of insulin-like growth factor-I gene transcription of osteoblasts. J Biol Chem, 1999, 274: 10609-10617.
189.Visek W J, Monroe R A, Swanson E W, Comar C L. Calcium metabolism in dairy cows as studied with Ca45. J Dairy Sci, 1953, 36: 373-383.
190.Wang L, Ma W, Markovich R, Chen J W, Wang P H. Regulation of cardiomyocyte apoptotic signaling by insulin-like growth factor I. Circ Res, 1998, 83:516-522.
191. Ward G, Harbers L H, Blaha J J. Calcium-containing crystals in alfalfa: Their fate in cattle. J Dairy Sci, 1979, 62: 715-722.
192.Ward G, Dobson R C, Dunham J R. Influences of calcium and phosphorus intakes, vitamin D supplementation, and lactation on calcium and phosphorus balances. J Dairy Sci, 1971, 55:768-776.
193.Wasserman R H, Taylor A N. Gastrointestinal absorption of calcium and phosphorus, in Handbook of physiology. In: Aubach G D ed., Sect. 7: Endocrinology. Vol. VII, Parathyroid gland. Washington DC: Am Physiol Soc, 1976. 137-155.
194.Wasserman R, Fullmer C S, Shimura F. Calcium absorption and the moleculareffects of vitamin D_3 in vitamin D. In: Kumar R ed., Basic and clinical aspects. Boston, MA: Martinus Nijhoff Publ, 1984. 233-258.
195.Wergedal J E, Baylink D J. Characterization of cells isolated and cultured from human bone. Pro Soc Exp Bio Med, 1984, 176: 60-69.
196.Yanpaisan W, King N J C, Doran P M. Flow cytometry of plant cells with applications in large-scale bioprocessings. Biotechnol Adv, 1999, 17: 3-27.
197.Yeh L C C, Adamo M L, Olson M S, Lee J C. Osteogenic protein-1 and insulin-like growth factor-1 synergistically stimulate rat osteoblastic cell differentiation and proliferation.Endocrinology,1997,138:4181-4190.
198.Yeh L C C,Lee J C,Co-transfection with the osteogenic protein(OP)-1 gene and the insulin-like growth factor(IGF)-1 gene enhanced osteoblastic cell differentiation.BBA-Molecular Cell Research,2006,1763:57-63.
199.Zhang K Q,Chen J W,Wang M L.The expression of insulin-like growth factor-1mRNA and polypeptide in rat osteoblasts with exposure to parathyroid hormone.Chinese Med J,2003,116:1916-1922.
200.Zhang X,Sobue T,Hurley M M.FGF-2 increases colony formation,PTH receptor,and IGF-I mRNA in mouse marrow stromal cells.Biochem Biophys Res Commun,2002,290:526-531.