孕激素受体在人牙周膜细胞中的表达及孕酮对细胞增殖和成骨分化影响的研究
|
摘要
绝经后骨质疏松症(osteoporosis, OP)是老年妇女的常见病,多发病。雌孕激素的缺乏被认为是绝经后骨质疏松的主要原因,而骨质疏松被认为是牙周病及牙齿缺失的原因之一。临床研究显示,牙槽骨高度及骨密度的降低与雌激素水平的降低有关。与雌激素相似,孕激素的水平在妇女绝经后也显著下降。孕酮具有重要的骨保护作用,以往的研究多集中于孕酮对全身骨骼系统的影响,而关于孕酮在牙槽骨改建中的作用及机制的研究甚少。
牙周膜(periodontal ligament cells,PDL)是牙骨质和牙槽骨之间的非矿化结缔组织。牙周膜能维持骨形成和骨吸收的平衡,在维持牙周组织内环境稳定中起重要的作用。因此,牙周膜是牙齿萌出和正畸牙移动的基础。人牙周膜细胞(human periodontal ligament cells,hPDLCs)来源于中胚层,它被认为是成骨细胞的来源且具有多向分化潜能。
孕酮是骨代谢的调节因子,它对牙周组组织也产生潜在的影响。孕酮水平的失衡也常常导致牙周疾病的发生。但hPDLCs是否表达孕激素受体(Progesterone receptor, PR),孕酮是否能影响hPDLCs的增殖及成骨分化仍不清楚。本实验主要是从基因和蛋白水平检测PR的表达,研究孕酮在hPDLCs增殖及成骨分化过程中的作用,进而为探讨孕激素及PR在牙槽骨吸收与改建中的作用机理奠定基础。
我们设计了如下实验:
1.人牙周膜细胞中孕激素受体的表达
取正畸拔除的健康前磨牙的牙周膜组织,进行hPDLCs的原代培养,用免疫细胞化学的方法检测PR蛋白的表达,RT-PCR的方法检测PR mRNA的表达。
2.孕酮对人牙周膜细胞增殖能力的影响
用含有不同浓度(1,10,100 nM)孕酮的培养液培养hPDLCs 1,2,3,4,5,6,7天,采用MTT的方法检测在孕酮作用下hPDLCs生长曲线的变化情况。用100 nM孕酮培养液培养hPDLCs3天,以流式细胞周期分析的方法检测孕酮作用下细胞周期的变化。分别以未作处理的hPDLCs作为空白对照组,特异性的PR拮抗剂RU486(100 nM)处理的hPDLCs为抑制剂组。
3.孕酮对人牙周膜细胞成骨作用的影响
我们研究了普通培养液和成骨诱导培养液中孕酮作用于细胞后碱性磷酸酶(Alkaline phosphatase,ALP)染色及茜素红染色钙化结节面积的变化。为了进一步研究孕酮在hPDLCs成骨分化中的作用,我们用孕酮干预hPDLCs,检测细胞ALP活性,检测骨涎蛋白(Bone sialoprotein ,BSP)、骨钙素(Osteocalcin,OCN)及骨桥蛋白(Osteopontin, OPN)的含量,研究孕酮及PR对hPDLCs成骨分化能力的影响。
4.雌孕激素联合对人牙周膜细胞增殖分化的影响
用雌二醇,孕酮及雌孕激素联合干预细胞。用MTT的方法检测雌孕激素对hPDLCs增殖的影响,用ALP活性分析和茜素红染色的方法检测雌孕激素对细胞成骨分化作用的影响。
5.孕酮对人牙周膜细胞c-fos、c-jun和Runx2基因表达的影响
用孕酮及抑制剂刺激hPDLCs,检测孕酮对细胞c-fos、c-jun和Runx2基因表达的影响。
研究结果发现:
1、免疫细胞化学结果显示,PR在hPDLCs的胞质和胞核中均有表达,且在胞核的表达明显高于胞质。RT-PCR结果显示hPDLCs中有PRmRNA的表达。
2、孕酮干预hPDLCs后,细胞的增殖高于对照组,PR抑制剂能明显抑制hPDLCs的生长。流式细胞周期分析结果显示:与对照组相比,孕酮组S+G2M期的百分比显著增加。抑制剂组的S+G2M期的百分比低于孕酮组,有显著差异。
3、在普通培养液中,孕酮组的ALP染色阳性面积和茜素红染色钙化结节面积明显高于对照组和抑制剂组。在成骨诱导液中,孕酮同样有促进成骨的作用。与成骨诱导组相比,诱导孕酮组的ALP染色阳性面积和茜素红染色钙化结节面积进一步增加。孕酮干预细胞后,hPDLCs中的ALP活性,BSP,OCN和OPN mRNA的表达升高具有时间及剂量依赖性,抑制剂组各指标减小。
4、在MTT分析中,对照组的hPDLCs增殖明显低于孕酮组、雌二醇组和雌孕联合组。但孕酮组、雌二醇组和雌孕联合组之间没有显著差异。茜素红染色结果显示,雌二醇组钙化结节面积高于孕酮组的钙化结节面积,两者的面积明显低于雌孕联合组。诱导雌孕组的钙化结节面积高于诱导孕酮组和诱导雌二醇组。雌孕联合组的ALP活性明显高于孕酮组和雌二醇组。
5、孕酮组c-fos、c-jun和Runx2 mRNA的表达明显高于对照组,而抑制剂组c-fos、c-jun和Runx2的表达显著降低。
得出了如下结论:
1、免疫细胞化学法和RT-PCR分别从蛋白水平和mRNA水平证实了PR在hPDLCs中有表达。
2、孕酮能够促进hPDLCs的增殖,孕激素受体拮抗剂能有效抑制hPDLCs的增殖。
3、孕酮能够促进hPDLCs的成骨分化,孕酮的作用能被孕激素受体抑制剂所拮抗。提示在hPDLCs的增殖和成骨分化中,孕酮是通过配体-受体途径来发挥其生物学效应的。
4、与空白对照组相比,孕酮、雌二醇及雌孕联合应用均能促进hPDLCs的增殖及成骨分化。雌孕激素联合应用与单独应用相比,对细胞增殖的影响没有显著差异。雌孕激素联合应用比单独应用能够进一步促进细胞的成骨分化。
5、孕酮能够上调hPDLCs中的c-fos、c-jun和Runx2 mRNA的表达。提示孕酮可能通过上调c-fos、c-jun和Runx2的表达促进hPDLCs的增殖和成骨分化,促进骨形成。
Postmenopausal osteoporosis (osteoporosis, OP) is a common and frequently-occurring disease for older women. Estrogen and progesterone deficiencies are well-known major contributors of postmenopausal osteoporosis development. Osteoporosis is regarded as one of the causes of periodontal disease and tooth loss. Clinical observations in postmenopausal women show that a higher frequency of loss of alveolar bone height as well as a low mandible bone density is accompanied by lower estrogen level. Similar to estrogen, the serum level of progesterone also reduces markedly after menopause. Recent experimental and clinical data have also demonstrated that progesterone plays a major role in protecting the skeleton. However, less information is available on the anabolic effects of progesterone on the remodeling of alveolar bone.
Periodontal ligament (PDL) is non-mineralized connective tissue located between the alveolar bone and cementum. PDL plays a vital role in maintaining homeostasis of periodontal tissues by affecting coordinated balance between bone formation and bone resorption activity. Thus, PDL is the fundamental requirement for both tooth eruption and orthodontic tooth movement. The periodontal ligament cells (PDLCs) are considered as multipotential cells and a source of osteoblasts.
As well as being the regulator of the integrity of the skeleton, progesterone has the potential effects on periodontal tissues. It is obvious that periodontal disease manifestations occur when an imbalance of progesterone takes place. However, it is still not clear whether progesterone receptor (PR) is expressed in hPDLCs and whether progesterone has effects on the proliferation and differentiation of hPDLCs. Therefore, the purpose of the present study is to detect the expression of PR in hPDLCs and explore the effects of progesterone on the proliferation and differentiation of hPDLCs in vitro. This research might lay the foundation for studying progesterone and the PR mechanism in the alveolar bone resorption and remodeling.
We designed and carried out the experiment as follows:
1. The expression of progesterone receptor in human periodontal ligament cells
The hPDL tissue was obtained from the extracted healthy premolar for orthodontic reasons. We performed the primary culture of hPDLCs. The PR expression in hPDLCs was detected by immunocytochemistry and the reverse transcriptase polymerase chain reaction.
2. The effect of progesterone on the proliferation of human periodontal ligament cells
The hPDLCs were stimulated with progesterone (1, 10, 100 nM) for 1, 2, 3, 4, 5, 6, and 7 days. MTT assay was performed to assess the effects of progesterone on cell growth curve. Cell cycle analysis was performed to further test the effect of 100 nM progesterone on the proliferation rate of hPDLCs by means of flow cytometry on the third day. The untreated hPDLCs served as control group. We employed RU486, a specific progesterone receptor antagonist, as antagonist group.
3. The effect of progesterone on the differentiation of human periodontal ligament cells
To quantify the effects of progesterone on osteogenic differentiation of hPDLCs, alizarin red and ALP staining were performed in basic culture medium and osteogenic medium. In this experiment we also examined the effect of the progesterone on ALP activity and the expression of BSP, OCN, and OPN mRNA in hPDLCs, respectively.
4. The effects of combined estrogen and progesterone on proliferation and differentiation of human periodontal ligament cells.
Cells were cultured in basic culture medium supplemented with progesterone, 17β-estrodiol or progesterone plus 17β-estrodiol. The effects of hormones on the proliferation were determined by MTT assay, and its effects on the differentiation were determined by alizarin red staining and ALP activity assay.
5. The effect of progesterone on the expression of c-fos、c-jun and Runx2 in human periodontal ligament cells.
Cells were untreated or treated with 100 nM progesterone in the absence or presence of 100 nM RU486.The expression of c-fos, c-jun mRNA were determined by RT-PCR. The effect of the progesterone on the expression of Runx2 mRNA in hPDLCs was determined by Realtime RT-PCR.
We found that:
1. In this study we proved the presence of PR mRNA in hPDLCs by using the RT-PCR and PR protein expression in hPDLCs by immunocytochemistry. The positive signal was strongly expressed in the nuclei but weaker in cytoplasm of hPDLCs.
2. Progesterone can promote the proliferation of hPDLCs. When RU486 was added, this action was blocked. The percentage of the cells in S + G2M phases was higher in progesterone-treated group than that in control group and progesterone + RU486 group.
3. In normal medium, the obvious mineralized nodules were detected in all the groups. The results showed that there were a few mineralized nodules in control group and progesterone + RU486 group. The amount of mineralized matrix increased in the progesterone-treated group. In osteogenic medium, increasing alizarin red–positive area was detected in osteogenic group, but the alizarin red–positive area was obviously less than that in osteogenic + progesterone group. The alizarin red–positive area was obviously decreased in osteogenic + progesterone + RU486 group. We got the similar result in ALP staining. The data have indicated that the progesterone can promote the ALP activity and the expression of BSP, OCN, and OPN mRNA in time- and dose-dependent manner in hPDLCs.
4. The proliferation of hPDLCs in control group was still lower than that in progesterone-treated group, estrodiol-treated group and estrogen- progesterone group. The difference among the groups treated with progesterone, estrodiol and estrodiol-progesterone is not significant. The alizarin red-positive area increased in the progesterone-estrogen group compared with progesterone-treated group and estrogen group, and the alizarin red-positive area was obviously increased in osteogenic + estrogen + progesterone group than that in osteogenic + estrogen and osteogenic + progesterone group. The results of ALP activity assay showed that the ALP activity was higher in estrogen-progesterone group compared with other three groups.
5. The results showed that the expression of c-fos, c-jun, and Runx2 mRNA was markedly enhanced in 100 nM Progesterone-treated group compared with control group, but decreased in progesterone + RU486 group.
In conclusion:
1. Our results demonstrate that the PR is expressed in hPDLCs at both mRNA and protein level.
2. Progesterone can stimulate the proliferation of the hPDLCs, and RU486 can block the effect of progesterone.
3. Progesterone can stimulate the differentiation of the hPDLCs, and RU486 can block the effect of progesterone. This also strongly supports the view that progesterone effects are mediated by the PR.
4. Estrogen and progesterone also can promote the proliferation and differentiation of hPDLCs. The effect of using estrogen and progesterone together on cell proliferation is not significantly different, compared with using estrogen and progesterone alone. Moreover, combined estrogen and progesterone can further promote the differentiation of hPDLCs compared with progesterone group and estrogen group.
5. Progesterone also can upregulate the expression of c-fos,c-jun, and Runx2 mRNA. Our current study suggested that progesterone may exert its bone-sparing functions by increasing the expression level of c-fos,c-jun, and Runx2 mRNA via PR in hPDLCs.
牙周膜(periodontal ligament cells,PDL)是牙骨质和牙槽骨之间的非矿化结缔组织。牙周膜能维持骨形成和骨吸收的平衡,在维持牙周组织内环境稳定中起重要的作用。因此,牙周膜是牙齿萌出和正畸牙移动的基础。人牙周膜细胞(human periodontal ligament cells,hPDLCs)来源于中胚层,它被认为是成骨细胞的来源且具有多向分化潜能。
孕酮是骨代谢的调节因子,它对牙周组组织也产生潜在的影响。孕酮水平的失衡也常常导致牙周疾病的发生。但hPDLCs是否表达孕激素受体(Progesterone receptor, PR),孕酮是否能影响hPDLCs的增殖及成骨分化仍不清楚。本实验主要是从基因和蛋白水平检测PR的表达,研究孕酮在hPDLCs增殖及成骨分化过程中的作用,进而为探讨孕激素及PR在牙槽骨吸收与改建中的作用机理奠定基础。
我们设计了如下实验:
1.人牙周膜细胞中孕激素受体的表达
取正畸拔除的健康前磨牙的牙周膜组织,进行hPDLCs的原代培养,用免疫细胞化学的方法检测PR蛋白的表达,RT-PCR的方法检测PR mRNA的表达。
2.孕酮对人牙周膜细胞增殖能力的影响
用含有不同浓度(1,10,100 nM)孕酮的培养液培养hPDLCs 1,2,3,4,5,6,7天,采用MTT的方法检测在孕酮作用下hPDLCs生长曲线的变化情况。用100 nM孕酮培养液培养hPDLCs3天,以流式细胞周期分析的方法检测孕酮作用下细胞周期的变化。分别以未作处理的hPDLCs作为空白对照组,特异性的PR拮抗剂RU486(100 nM)处理的hPDLCs为抑制剂组。
3.孕酮对人牙周膜细胞成骨作用的影响
我们研究了普通培养液和成骨诱导培养液中孕酮作用于细胞后碱性磷酸酶(Alkaline phosphatase,ALP)染色及茜素红染色钙化结节面积的变化。为了进一步研究孕酮在hPDLCs成骨分化中的作用,我们用孕酮干预hPDLCs,检测细胞ALP活性,检测骨涎蛋白(Bone sialoprotein ,BSP)、骨钙素(Osteocalcin,OCN)及骨桥蛋白(Osteopontin, OPN)的含量,研究孕酮及PR对hPDLCs成骨分化能力的影响。
4.雌孕激素联合对人牙周膜细胞增殖分化的影响
用雌二醇,孕酮及雌孕激素联合干预细胞。用MTT的方法检测雌孕激素对hPDLCs增殖的影响,用ALP活性分析和茜素红染色的方法检测雌孕激素对细胞成骨分化作用的影响。
5.孕酮对人牙周膜细胞c-fos、c-jun和Runx2基因表达的影响
用孕酮及抑制剂刺激hPDLCs,检测孕酮对细胞c-fos、c-jun和Runx2基因表达的影响。
研究结果发现:
1、免疫细胞化学结果显示,PR在hPDLCs的胞质和胞核中均有表达,且在胞核的表达明显高于胞质。RT-PCR结果显示hPDLCs中有PRmRNA的表达。
2、孕酮干预hPDLCs后,细胞的增殖高于对照组,PR抑制剂能明显抑制hPDLCs的生长。流式细胞周期分析结果显示:与对照组相比,孕酮组S+G2M期的百分比显著增加。抑制剂组的S+G2M期的百分比低于孕酮组,有显著差异。
3、在普通培养液中,孕酮组的ALP染色阳性面积和茜素红染色钙化结节面积明显高于对照组和抑制剂组。在成骨诱导液中,孕酮同样有促进成骨的作用。与成骨诱导组相比,诱导孕酮组的ALP染色阳性面积和茜素红染色钙化结节面积进一步增加。孕酮干预细胞后,hPDLCs中的ALP活性,BSP,OCN和OPN mRNA的表达升高具有时间及剂量依赖性,抑制剂组各指标减小。
4、在MTT分析中,对照组的hPDLCs增殖明显低于孕酮组、雌二醇组和雌孕联合组。但孕酮组、雌二醇组和雌孕联合组之间没有显著差异。茜素红染色结果显示,雌二醇组钙化结节面积高于孕酮组的钙化结节面积,两者的面积明显低于雌孕联合组。诱导雌孕组的钙化结节面积高于诱导孕酮组和诱导雌二醇组。雌孕联合组的ALP活性明显高于孕酮组和雌二醇组。
5、孕酮组c-fos、c-jun和Runx2 mRNA的表达明显高于对照组,而抑制剂组c-fos、c-jun和Runx2的表达显著降低。
得出了如下结论:
1、免疫细胞化学法和RT-PCR分别从蛋白水平和mRNA水平证实了PR在hPDLCs中有表达。
2、孕酮能够促进hPDLCs的增殖,孕激素受体拮抗剂能有效抑制hPDLCs的增殖。
3、孕酮能够促进hPDLCs的成骨分化,孕酮的作用能被孕激素受体抑制剂所拮抗。提示在hPDLCs的增殖和成骨分化中,孕酮是通过配体-受体途径来发挥其生物学效应的。
4、与空白对照组相比,孕酮、雌二醇及雌孕联合应用均能促进hPDLCs的增殖及成骨分化。雌孕激素联合应用与单独应用相比,对细胞增殖的影响没有显著差异。雌孕激素联合应用比单独应用能够进一步促进细胞的成骨分化。
5、孕酮能够上调hPDLCs中的c-fos、c-jun和Runx2 mRNA的表达。提示孕酮可能通过上调c-fos、c-jun和Runx2的表达促进hPDLCs的增殖和成骨分化,促进骨形成。
Postmenopausal osteoporosis (osteoporosis, OP) is a common and frequently-occurring disease for older women. Estrogen and progesterone deficiencies are well-known major contributors of postmenopausal osteoporosis development. Osteoporosis is regarded as one of the causes of periodontal disease and tooth loss. Clinical observations in postmenopausal women show that a higher frequency of loss of alveolar bone height as well as a low mandible bone density is accompanied by lower estrogen level. Similar to estrogen, the serum level of progesterone also reduces markedly after menopause. Recent experimental and clinical data have also demonstrated that progesterone plays a major role in protecting the skeleton. However, less information is available on the anabolic effects of progesterone on the remodeling of alveolar bone.
Periodontal ligament (PDL) is non-mineralized connective tissue located between the alveolar bone and cementum. PDL plays a vital role in maintaining homeostasis of periodontal tissues by affecting coordinated balance between bone formation and bone resorption activity. Thus, PDL is the fundamental requirement for both tooth eruption and orthodontic tooth movement. The periodontal ligament cells (PDLCs) are considered as multipotential cells and a source of osteoblasts.
As well as being the regulator of the integrity of the skeleton, progesterone has the potential effects on periodontal tissues. It is obvious that periodontal disease manifestations occur when an imbalance of progesterone takes place. However, it is still not clear whether progesterone receptor (PR) is expressed in hPDLCs and whether progesterone has effects on the proliferation and differentiation of hPDLCs. Therefore, the purpose of the present study is to detect the expression of PR in hPDLCs and explore the effects of progesterone on the proliferation and differentiation of hPDLCs in vitro. This research might lay the foundation for studying progesterone and the PR mechanism in the alveolar bone resorption and remodeling.
We designed and carried out the experiment as follows:
1. The expression of progesterone receptor in human periodontal ligament cells
The hPDL tissue was obtained from the extracted healthy premolar for orthodontic reasons. We performed the primary culture of hPDLCs. The PR expression in hPDLCs was detected by immunocytochemistry and the reverse transcriptase polymerase chain reaction.
2. The effect of progesterone on the proliferation of human periodontal ligament cells
The hPDLCs were stimulated with progesterone (1, 10, 100 nM) for 1, 2, 3, 4, 5, 6, and 7 days. MTT assay was performed to assess the effects of progesterone on cell growth curve. Cell cycle analysis was performed to further test the effect of 100 nM progesterone on the proliferation rate of hPDLCs by means of flow cytometry on the third day. The untreated hPDLCs served as control group. We employed RU486, a specific progesterone receptor antagonist, as antagonist group.
3. The effect of progesterone on the differentiation of human periodontal ligament cells
To quantify the effects of progesterone on osteogenic differentiation of hPDLCs, alizarin red and ALP staining were performed in basic culture medium and osteogenic medium. In this experiment we also examined the effect of the progesterone on ALP activity and the expression of BSP, OCN, and OPN mRNA in hPDLCs, respectively.
4. The effects of combined estrogen and progesterone on proliferation and differentiation of human periodontal ligament cells.
Cells were cultured in basic culture medium supplemented with progesterone, 17β-estrodiol or progesterone plus 17β-estrodiol. The effects of hormones on the proliferation were determined by MTT assay, and its effects on the differentiation were determined by alizarin red staining and ALP activity assay.
5. The effect of progesterone on the expression of c-fos、c-jun and Runx2 in human periodontal ligament cells.
Cells were untreated or treated with 100 nM progesterone in the absence or presence of 100 nM RU486.The expression of c-fos, c-jun mRNA were determined by RT-PCR. The effect of the progesterone on the expression of Runx2 mRNA in hPDLCs was determined by Realtime RT-PCR.
We found that:
1. In this study we proved the presence of PR mRNA in hPDLCs by using the RT-PCR and PR protein expression in hPDLCs by immunocytochemistry. The positive signal was strongly expressed in the nuclei but weaker in cytoplasm of hPDLCs.
2. Progesterone can promote the proliferation of hPDLCs. When RU486 was added, this action was blocked. The percentage of the cells in S + G2M phases was higher in progesterone-treated group than that in control group and progesterone + RU486 group.
3. In normal medium, the obvious mineralized nodules were detected in all the groups. The results showed that there were a few mineralized nodules in control group and progesterone + RU486 group. The amount of mineralized matrix increased in the progesterone-treated group. In osteogenic medium, increasing alizarin red–positive area was detected in osteogenic group, but the alizarin red–positive area was obviously less than that in osteogenic + progesterone group. The alizarin red–positive area was obviously decreased in osteogenic + progesterone + RU486 group. We got the similar result in ALP staining. The data have indicated that the progesterone can promote the ALP activity and the expression of BSP, OCN, and OPN mRNA in time- and dose-dependent manner in hPDLCs.
4. The proliferation of hPDLCs in control group was still lower than that in progesterone-treated group, estrodiol-treated group and estrogen- progesterone group. The difference among the groups treated with progesterone, estrodiol and estrodiol-progesterone is not significant. The alizarin red-positive area increased in the progesterone-estrogen group compared with progesterone-treated group and estrogen group, and the alizarin red-positive area was obviously increased in osteogenic + estrogen + progesterone group than that in osteogenic + estrogen and osteogenic + progesterone group. The results of ALP activity assay showed that the ALP activity was higher in estrogen-progesterone group compared with other three groups.
5. The results showed that the expression of c-fos, c-jun, and Runx2 mRNA was markedly enhanced in 100 nM Progesterone-treated group compared with control group, but decreased in progesterone + RU486 group.
In conclusion:
1. Our results demonstrate that the PR is expressed in hPDLCs at both mRNA and protein level.
2. Progesterone can stimulate the proliferation of the hPDLCs, and RU486 can block the effect of progesterone.
3. Progesterone can stimulate the differentiation of the hPDLCs, and RU486 can block the effect of progesterone. This also strongly supports the view that progesterone effects are mediated by the PR.
4. Estrogen and progesterone also can promote the proliferation and differentiation of hPDLCs. The effect of using estrogen and progesterone together on cell proliferation is not significantly different, compared with using estrogen and progesterone alone. Moreover, combined estrogen and progesterone can further promote the differentiation of hPDLCs compared with progesterone group and estrogen group.
5. Progesterone also can upregulate the expression of c-fos,c-jun, and Runx2 mRNA. Our current study suggested that progesterone may exert its bone-sparing functions by increasing the expression level of c-fos,c-jun, and Runx2 mRNA via PR in hPDLCs.
引文
[1] Dervis E. Oral implications of osteoporosis [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2005,100 (3):349– 356.
[2]邵敬於。性激素的临床应用,复旦大学出版社.
[3]丰有占,沈铿。妇产科学人民卫生出版社.
[4] Yen. SS: The Human Menstrual Cycle: Neuroendocrine Regulation. Reproductive Endocrinology, 1991a, 3rd edition, 276.
[5] Mariotti A. Sex steroid hormones and cell dynamics in the periodontium. Crit Rev Oral Biol Med [J]. 1994, 5(1):27-53.
[6] Evans RM. The steroid and thyroid hormone receptors superfamily [J]. Science, 1988, 240:889-895.
[7] Wei LL, Sheridan PL, Krett NL, et al. Immunologic analysis of human breast cancer progesterone receptors. 2. Structure, phosphorylation, and processing [J]. Biochemistry, 1987, 26(19): 6262-6272.
[8] Wei LL and Horwitz KB. The structure of progesterone receptors [J]. Steroids, 1985, 46(2-3):677-695.
[9] Tung L, Mohamed MK: Hoefiler JP et al. Antagonist-occupied human progesterone Breceptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors [J]. Mol. EndocrinoL, 1993, 7(10): 1256-1265.
[10] Vegeto E, Shahbaz MM, Wen DX, et al. Human progesterone receptor A form is a cell-and promoter-specific repressor of human progesterone receptor B function [J]. Mol. Endocrinol, 1993, 7(10): 1244-1255.
[11] Wen DX, Xu YF, Mais DE, et al. The A and B isoforms of the humanprogesterone receptor operate through distinct signaling pathways within target cells [J ]. MoL Cell. Biol. 1994, 14(12): 8356-8364.
[12] Wei LL, Norris BM, Baker CJ. An N-terminally truncated third progesterone receptor protein, PR(C), forms heterodimers with PR(B) but interferes in PR(B)-DNA binding [J]. J Steroid Biochem Mol Biol. 1997, 62(4):287-297.
[13] Perrot-Applanat M, Logeat F, Groyer-Picard MT, et al. Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies [J ]. Endocrinology, 1985, 116(4):1473-1484.
[14] Duffy DM, Stouffer RL.Progesterone receptor messenger ribonucleic acid in the primate corpus luteum during the menstrual cycle: possible regulation by progesterone [J]. Endocrinology, 1995,136(5):1869-1876.
[15] Batra S, Iosif S. Progesterone receptors in human vaginal tissue [J]. Am J Obstet Gynecol, 1985, 153(5):524-528.
[16] Terner C. Progesterone and progestins in the male reproductive system [J]. Ann N Y Acad Sci. 1977, 286:313-320.
[17] Perrot-Applanat M, Groyer-Picard MT, Lorenzo F, et al. Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors [J]. Cancer Res, 1987, 47(10):2652-2661.
[18] Perrot-Applanat M, Cohen-Solal K, Milgrom E, et al. Progesterone receptors expression in human saphenous veins [J]. Circulation, 1995(10), 92:2975-2983.
[19] Kawahara K, Shimazu A. Expression and intracellular localization of progesterone receptors in cultured human gingival fibroblasts [J]. J Periodontal Res, 2003, 38(3):242-246.
[20] MacNamara P, O'Shaughnessy C, Manduca P, et al. Progesteronereceptors are expressed in Human osteoblast-like cell lines and in primary human osteoblast cultures [J]. Calcif Tissue Int, 1995, 57(6):436-441.
[21] Gorski J, Toft D, Shyamala G, et al. Hormone Receptors: Studies on the Interaction of Estrogen with the Uterous [J]. Recent Prog. Horm. Res, 1968, 24:45-80.
[22] Jensen EV, Suzuki T, Kawashima T, et al. A Two-Step Mechanism for the Interaction of Estradiol with Rat Uterous [J]. Proc. Natl. Acad. Sci. U.S.A, 1968, 59:632-638.
[23] Dijkema R,Sehoonen WG,Teuwen R,et al. Human progesterone receptor A and B isoforms in CHO cells. I. Stable transfection of receptor and receptor-responsive reporter genes: transcription modulation by (anti)progestagens [J]. J Steroid Biochem Mol Biol, 1998, 64(3-4): 147-156.
[24] Kumar NS,Richer J,Owen G,et al. Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action [J]. Cancer Res,1998,58(9):1860-1865.
[25] Rickard D, Harris SA, Turner R, et al. Estrogen and Progesterone [M] .Principles of Bone Biology, second edition, 668.
[26] Clark JH, Schrader WT, O'Malley BW: Mechanism of Action of Steroid Hormones [M]. Williams Textbook of Endocrinology, 1992, 8th edition, 36.
[27] Evans RM. The steroid and thyroid hormone receptor superfamily [J].Science 240 1988, 240: 889-895.
[28] Tsai MJ, O'Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members [J]. Annu Rev Biochem, 1994, 63: 451-486.
[29] Bramley T. Non-genomic progesterone receptors in the mammalian ovary:some unresolved issues [J]. Reproduction 2003, 125(1):3–15.
[30] Gerdes D, Christ M, Haseroth K, et al. Nongenomic actions of steroids-from laboratory to clinical implications [J].J Paediatr Endocrinol Metab, 2000, 13(7):853–878.
[31] Grosse B, Kachkache M, Le Mellay V, et al. Membrane signalling and progesterone in female and male osteoblasts. I. Involvement of intracellular Ca2+, inositol trisphosphate, and diacylglycerol, but not cAMP [J]. J Cell Biochem, 2000, 79(2):334-345.
[32] Boonyaratanakornkit V, Scott MP, Ribon V, et al. Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases [J]. Mol Cell, 2001, 8(2):269-280.
[33] Anonymous. Osteoporosis prevention, diagnosis and therapy. NIH Consens Statement, 2000, 17: 1 - 45.
[34] Riggs BL. Overview of osteoporosis [J]. West J Med. 1991, 154(1): 63–77.
[35] Payne JB, Reinhardt RA, Nummikoski PV. Longitudinal alveolar bone loss in postmenopausal osteoprorotic/osteopenic women [J]. Osteoporos Int, 1999, 10(1):34-40.
[36] Wells G, Cranney A, Peterson J, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women [J]. Cochrane Database Syst Rev. 2008 Jan 23, (1):CD004523.
[37] McCabe LR, Last TJ , Lynch M, et al. Expression of cell growth and bone phenotypic genes during the cell cycle of normal diploid osteoblasts and osteo sarcoma cells [J]. J Cell Biochem, 1994, 56(2): 274-282.
[38] Zheng MH, Wood DJ, Papadimitriou JM. What′s new in the role of cytokines on osteoblast proliferation and differentiation [J]. Pathol Res Pract, 1992, 188(8): 1104-1121.
[39] Owen TA, Aronow M, Shalhoub V, et al. Progressive development of the rat o steoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix [J]. J Cell Physiol, 1990, 143(3): 420-430.
[40] Lerner UH. Bone remodeling in post-menopausal osteoporosis [J]. J Dent Res, 2006, 85(7):584-595.
[41] Albright F, Smith PH, and Richardson AM. Post-menopausal osteoporosis: Its clinical features. J Am Med Assos, 1941, 116:2465-2474.
[42] Burnett, CC, and Reddi AH. Influence of estrogen and progesterone on matrix-induced endochondral bone formation [J]. Calcif Tissue Int, 1983, 35(4-5):609-614.
[43] Snow, GR, and Anderson C. The effects of continuous progesterone treatment on cortical bone remodeling activity in beagles [J]. Calcif Tissue Int. 1985, 37(3): 282- 286.
[44] Barengolts EI, Gajardo HF, Rosol TJ, et al. Effects of progesterone on postovariectomy bone loss in aged rats [J]. J Bone Miner Res, 1990, 5(11):1143-1147.
[45] Barengolts, EI, Kouznetsova T, Segalene A, et al. Effects of progesterone on serum levels of IGF-1 and on femur IGF-1 mRNA in ovariectomized rats [J]. J Bone Miner Res, 1996, 11(10): 1406-1412.
[46] Prior JC, Vigna YM, Barr SI, et al. Cyclic medroxyprogesterone treatment increases bone density: A controlled trial in active women with menstrual cycle disturbances [J]. Am J Med, 1994, 96(6): 521-530.
[47] McNeeley SG Jr, Schinfeld JS, Stovall TG, et al. Prevention of osteoporosis by medroxyprogesterone acetate in postmenopausal women [J]. Int J Gynaecol Obstet, 1991, 34(3):253-256.
[48] Grey A, Cundy T, Evans M, et al. Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post- menopausal women [J]. Clin. Endocrinol. 1996, 44(3): 293-296.
[49] Gallagher JC, Kable WT, Goldgar D. Effect of progestin therapy on cortical and trabecular bone: Comparison with estrogen [J]. Am J Med, 1991, 90(2): 171-178.
[50] Grecu EO, Weinshelbaum A, Simmons R. Effective therapy of glucocorticoid-induced osteoporosis with methoxyprogesterone acetate [J]. Calcif Tissue Int, 1990, 46(5):294-299.
[51] Gbolade B, Ellis S, Murby B, et al. Bone density in long term users of depot medroxyprogesterone acetate [J]. Br J Obstet Gynaecol. 1998, 105(7): 790-794.
[52] Parfitt AM. What is the normal rate of bone remodeling? [J]. Bone, 2004, 35(1):1-3.
[53] Boivin G, Anthoine-Terrier C, Morel G. Ultrastructural localization of endogenous hormones and receptors in bone tissue: an immunocytological approach in frozen samples [J]. Micron. 1994, 25(1):15-27.
[54] Tremollieres FA, Strong DD, Baylink DJ, et al. Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production [J]. Acta Endocrinol, 1992, 126(4): 329-337.
[55]梁敏.孕酮和18-甲左炔诺孕酮对成骨细胞作用机制的研究.中南大学博士学位论文.
[56] Verharr HJ, Damen CA, Duursma SA, et al. A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro. Bone, 1994, 15(3):307-311.
[57] Luo XH, Liao EY, Su X. Progesterone upregulates TGF-βisoforms (β1,β2, andβ3) expression in normal human osteoblast- like cells [J]. Calcif Tissue Int, 2002, 71(4):329-334.
[58] Girasole G, Jilka RL Passeri G, et al. 17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens [J]. J Clin Invest, 1992, 89(3): 883-891.
[59] Huang QX, Zhou HD, Liao EY, et al. Effects of estradiol and progesterone on the expression of insulin receptor substrate in human osteoblasts [J]. Zhonghua Yi Xue Za Zhi, 2005, 85(11):743-746.
[60] Luo XH, Liao EY. Progesterone differentially regulates the membrane- type matrix metalloproteinase-1 (MT1-MMP) compartment of proMMP-2 activation in MG-63 cells [J]. Horm Metab Res 2001, 33(7): 383-388.
[61] Ishida Y, Bellows CG, Tertinegg I, et al. Progesterone-mediated stimulation of osteoprogenitor proliferation and differentiation in cell populations derived from adult or fetal rat bone tissue depends on the serum component of the culture media [J]. Osteoporos Int, 1997, 7(4):323-330.
[62] Günhan M, Günhan O, Celasun B,et al. Estrogen and progesterone receptors in the peripheral giant cell granulomas of the oral cavity[J]. J Oral Sci, 1998, 40(2):57-60.
[63] Liao EY, Luo XH, Su X. Comparison of the effects of 17beta-E2 and progesterone on the expression of osteoprotegerin in normal human osteoblast-like cells [J]. J Endocrinol Invest. 2002, 25(9):785-90.
[64] Canalis E and Raisz LG. Effect of sex steroids on bone collagen synthesis in vitro [J]. Calcif Tissue Res. 1978, 25(2):105-110.
[65] Scheven BA, Damen CA, Hamilton NJ, et al. Stimulatory effects ofestrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro [J]. Biochem Biophys Res Commun, 1992, 186(1):54–60.
[66] Slootweg MC, Ederveen AG, Schot LP, et al. Oestrogen and progesterone synergistically stimulate human and rat osteoblast proliferation [J]. J Endocrinol, 1992, 133(2): R5-R8.
[67] Lu CC, Tsai SC, Wang SW, et al. Effects of ovarian steroid hormones and thyroxine on calcitonin secretion in pregnant rats [J]. Am J Physiol, 1998, 274(2 Pt 1):E246-252.
[68] Jeffcoate W. Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency [J] .Ann Clin Biochem, 1999, 36(Pt2):151-157.
[69] Nelson HD, Humphrey LL, Nygren P, et al. Postmenopausal hormone replacement therapy: scientific review. JAMA, 2002, 288(7):872-881.
[70] Yamamoto Y, Kurabayashi T, Tojo Y, et al. Effects of progestins on the metabolism of cancellous bone in aged oophorectomized rats [J]. Bone, 1998, 22(5):533-537.
[71] Ishida Y and Heersche JN. Progesterone- and dexamethasone-dependent osteoprogenitors in bone cell populations derived from rat vertebrae are different and distinct [J]. Endocrinology, 1999, 140(7): 3210-3218.
[72] Gunnet JW, Granger K, Cryan E, et al. Characterization of the progestin receptors in the human TE85 and murine MC3T3-E1 osteoblast-like cell lines [J].J Endocrinol, 1999, 163(1):139-147.
[73] Eriksen EF, Colvard DS, Berg NJ, et al. Evidence of estrogen receptors in normal human osteoblast-like cells [J]. Science, 1988, 241(4861): 84-86.
[74] Harris SA, Tau KR, Enger RJ, et al. Estrogen response in the hFOB 1.19 human fetal osteoblastic cell line stably transfected with the humanestrogen receptor gene [J]. J Cell Biochem, 1995, 59(2), 193- 201.
[75] Mac Namara P and Loughrey HC. Progesterone receptor A and B isoforms in human osteoblasts [J]. Calcif Tissue Int, 1998, 63(1): 39-46.
[76] Schmidt IU, Wakley GK, Turner RT. Effects of estrogen and progesterone on tibia histomorphometry in growing rats [J]. Calcif Tissue Int, 2000, 67(1):47-52.
[77] Delaveyne-Bitbol R, Garabedian M. In vitro responses to 17beta-estradiol throughout pubertal maturation in female human bone cells [J]. J Bone Miner Res, 1999, 14(3):376-385.
[78] Mizunuma H, Okano H, Soda M, et al. Prevention of postmenopausal bone loss with minimal uterine bleeding using low dose continuous estrogen/ progestin therapy: a 2-year prospective study [J] .Maturitas, 1997, 27(1): 69-76.
[79] Jeffcoat MK. Bone loss in the oral cavity [J]. J Bone Min Res, 1993, 8 suppl: S467-473.
[80] Streckfus CF , Johnson RB , Nick T, et al . Comparison of alverolar bone loss, alverlar bone density and second metacarpal bone dentisy, salivary and gingival crevicular fluid interleukin-6 concentrations in healthy premenopausal and postmenopausal women on estrogen therapy [J]. J Gerontol Biol A Sci Med Sci, 1997, 52(6): M343-351.
[81] Elovic RP, Hipp JA, Hayes WC. Maxillary molar extraction causes increased bone loss in the mandible of ovariectomized rats [J]. J bone Miner Res, 1995, 10 (7):1087-1093.
[82] Bollen AM, Taguchi A, Hujoel PP, et al. Case-control study on self- reported osteoporotic fractures and mandibular cortical bone [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000, 90(4): 518-524.
[83] Tezal M, Wactawski-Wende J , Grossi SG, et al . The relationship between bone mineral density and periodontitis in postmenopausal women. J Periodontol, 2000, 71(9):1492-1498.
[84] Dumitrescu AL. Occurrence of self-reported systemic medical conditions in patients with periodontal disease [J]. Rom J Intern Med, 2006, 44(1): 35-48.
[85] Otogoto J, Ota N. Correlation between periodontal disease and osteoporosis using panoramic radiographic parameters for diagnosed osteoporosis in dental clinic [J]. Clin Calcium, 2003, 13(5): 582-586.
[86] Famili P, Cauley J, Suzuki JB, et al. Longitudinal study of periodontal disease and edentulism with rates of bone loss in older women. J Periodontol, 2005, 76(1):11-15.
[87] Pilgram TK, Hildebolt CF, Dotson M, et al. Relationships between clinical attachment level and spine and hip bone mineral density: data from healthy postmenopausal women [J]. J Periodontol, 2002, 73(3): 298-301.
[88]张铭.妊娠期大鼠正畸力刺激下牙周组织中雌、孕激素受体表达变化的实验研究.四川大学口腔医学博士专业论文.
[89] Tilakaratne A, Soory M, Ranasinghe AW,et al. Periodontal disease status during pregnancy and 3 months post-partum, in a rural population of Sri-Lankan women[J]. J Clin Periodontol, 2000, 27(10):787-792.
[90] Kornman KS, Loesche WJ. The subgingival microbial flora during pregnancy [J]. J Periodontal Res, 1980, 15(2):111-122.
[91] Tsai CC, Chen KS. A study on sex hormones in gingival crevicular fluid and black pigmented bacteria in subgingival plaque of pregnant women [J]. Gaoxiong Yi Xue Ke Xue Za Zhi, 1995, 11(5):265-273.
[92] Lapp CA,Lohse JE,Lewis JB, et al. The effects of progesterone on matrixmetalloproteinases in cultured human gingival fibroblasts [J]. J Periodontol, 2003, 74(3):277-288.
[93] Hellsing E, Hammarstr?m L. The effects of pregnancy and fluoride on orthodontic tooth movements in rats [J]. Eur J Orthod, 1991, 13(3):223-230.
[94] Gould TR, Melcher AH, Brunette DM. Migration and division of progenitor cell populations in periodontal ligament after wounding [J]. J Periodont Res, 1980, 15(1):20-42.
[95] Morishita M, Yamamura T, Bachchu MA, et al. The effects of oestrogen on osteocalcin production by human periodontal ligament cells [J]. Arch Oral Biol, 1998, 43(4):329-333.
[96] Nojima N, Kobayashi M, Shionome M, et al. Fibroblastic cells derived from bovine periodontal ligaments have the phenotypes of osteoblasts [J]. J Periodontal Res, 1990, 25(3):179-185.
[97] Somerman MJ,Archer SY,Imm GR. Comparative study of human periodontal ligament cells and gingival fibroblasts in vitro [J]. J Dent Res, 1988, 67(1):66-70.
[98] Guiochon-Mantel A,Lescop P,Christin-Maitre S, et al. Nucleocytoplasmic shuttling of the progesterone receptor [J]. EMBO J, 1991, 10(12): 3851- 3859.
[99] J?nsson D, Wahlin ?, Idvall I, et al. Differential effects of estrogen on DNA synthesis in human periodontal ligament and breast cancer cells [J]. J Periodontal Res, 2005, 40(5): 401-406.
[100] Amar S, Chung KM. Clinical implications of cellular biologic advances in periodontal regeneration [J] .Curr Opin Periodontol,1994,18(2):128-140.
[101] Ishida Y, Heersche JN. Progesterone stimulates proliferation anddifferentiation of osteoprogenitor cells in bone cell populations derived from adult female but not from adult male rats [J]. Bone, 1997, 20(1):17-25.
[102]陈璐璐,Scholler J,Fpged NT.孕酮对离体胎鼠头盖骨成骨细胞增殖与分化的影响[J].中华妇产科杂志,1997,32(9):538-540.
[103] Lekic P, Rojas J, Birek C, et al. Phenotypic comparison of periodontal ligament cells in vivo and in vitro[J]. J Periodontal Res, 2001, 36(2):71-79.
[104] Lekic P,McCulloch CA. Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue [J]. Anat Rec.1996, 245(2):327-341.
[105] Shimizu Y, Inomata Y, Tagami A. Suppression of osteoclast-like cell formation by periodontal ligament cells [J]. J Bone Miner Metab, 1996, 14:65-72.
[106] Arceo N, Sauk JJ, Moehring J, et al. Human periodontal cells initiate mineral-like nodules in vitro[J]. J Periodontol, 1991, 62(8):499-503.
[107] Lang H, Schuler N, Arnhold S, et al. Formation of differentiated tissues in vivo by periodontal cell populations cultured in vitro [J]. J Dent Res, 1995, 74(5):1219-1225.
[108] Lindskog S, Bloml L. Quality of periodontal healing. IV: enzyme histochemical evidence for an osteoblast origin of reparative cementum [J]. Swed Dent J, 1994, 18(5): 181-189.
[109] Mukai M, Yoshimine Y, Akamine A, et al. Bone-like nodules formed in vitro by rat periodontal ligament cells [J]. Cell Tissue Res, 1993, 271(3): 453-460.
[110] Morishita M, Yamamura T, Shimazu A, et al. Estradiol enhances theproduction of mineralized nodules by human periodontal ligament cells [J]. J Clin Periodontol, 1999, 26(11):748-751.
[111] Quarles LD, Yohay DA, Lever LW,et al. Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development [J]. J Bone Miner Res, 1992, 7(6): 683-692.
[112] Pavlin D, Dove SB, Zadro R,et al. Mechanical loading stimulates differentiation of periodontal osteoblasts in a mouse osteoinduction model: effect on type I collagen and alkaline phosphatase genes [J]. Calcif Tissue Int, 2000, 67(2):163-172.
[113] Goseki M, Oida S, Takeda K, et al. Identification of bone-type alkaline phosphatase mRNA from human periodontal ligament cells [J]. J Dent Res, 1995, 74(1):319–322.
[114] Groeneveld MC, Everts V, Beertsen W. Alkaline phosphatase activity in the periodontal ligament and gingiva of the rat molar: its relation to cementum formation [J]. J Dent Res, 1995, 74(7):1374–1381.
[115] Ogata Y, Niisato N, Sakurai T,et al. Comparison of characteristics of human gingival fibroblasts and periodontal ligament cells [J]. J Periodontol, 1995, 66(12):1025-1031.
[116] Murakami Y, Kojima T, Nagasawa T,et al. Novel isolation of alkaline phosphatase-positive subpopulation from periodontal ligament fibroblasts [J]. J Periodontol, 2003, 74(6): 780-786.
[117] Isaka J, Ohazama A, Kobayashi M, et al. Participation of periodontal ligament cells with regeneration of alveolar bone [J]. J Periodontol, 2001, 72(3): 314-323.
[118] Bellahcène A, Antoine N, Clausse N, et al. Detection of bone sialoproteinin human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels [J]. Lab Invest, 1996, 75(2):203-210.
[119] Chen J, Shapiro H, Sodek J. Development expression of bone sialoprotein mRNA in rat mineralized connective tissues [J]. J Bone Miner Res, 1992, 7(8):987-997.
[120] Kobayashi D, Takita H, Mizuno M, et al. Time-dependent expression of bone sialoprotein fragments in osteogenesis induced by bone morphogenetic protein [J]. J Biochem. 1996, 119(3):475-481.
[121] Cho P, Schneider GB, Krizan K, et al. Examination of the bone-implant interface in experimentally induced osteoporotic bone [J]. Implant Dent, 2004, 13(1):79-87.
[122] Chien HH, Lin WL, Cho MI. Expression of TGF-beta isoforms and their receptors during mineralized nodule formation by rat periodontal ligament cells in vitro [J]. J Periodontal Res. 1999, 34(6):301-309.
[123] Lekic P, Sodek J, McCulloch CA. Osteopontin and bone sialoprotein expression in regenerating rat periodontal ligament and alveolar bone [J]. Anat Rec. 1996, 244(1):50-58.
[124] Domon S, Shimokawa H, Yamaguchi S, et al. Temporal and spatial mRNA expression of bone sialoprotein and type I collagen during rodent tooth movement [J]. Eur J Orthod, 2001, 23(4):339-348.
[125] Hauschka PV. Osteocalcin: the vitamin K-dependent Ca2+- binding protein of bone matrix [J]. Haemostasis, 1986, 16(3-4):258–272.
[126] Liang L, Yu JF, Wang Y, Wang G, Ding Y. Effect of estrogen receptor beta on the osteoblastic differentiation function of human periodontal ligament cells [J]. Arch Oral Biol, 2008, 53(6):553-557.
[127] Goldsmith HL, Labrosse JM, Mclntosh FA, et al. Homotypic interactionsof soluble and immobilized osteopontin [J]. Ann Biomed Eng, 2002, 30(6):840-850.
[128] Noda M, Tsuji K, Nifuji A. Osteopontin: a topic from the point of bone morphology [J]. Clin Calcium, 2003, 13(4):464-466.
[129] Wan YM, Ma YJ, Zhang XY, et al. Effects of rotation on osteonectin and osteopontin mRNA level of cultured osteoblasts in rats. Sheng Li Xue Bao, 2005, 57(3):384-388.
[130] Johnson GA, Spencer TE, Burghardt RC, et al. Progesterone modulation of osteopontin gene expression in the ovine uterus [J]. Biol Reprod, 2000, 62(5):1315-1321.
[131] Lin DG, Kenny DJ, Barrett EJ. Storage conditions of avulsed teeth affect the phenotype of cultured human periodontal ligament cells [J]. J Periodontal Res, 2000, 35(1):42-50.
[132] Wactawski-Wende J, Hausmann E, Hovey K, et al. The association between osteoporosis and alveolar crestal height in postmenopausal women [J]. J Periodontol, 2005, 76(11 Suppl):2116-2124.
[133] Reinhardt RA, Payne JB, Maze CA. Influence of estrogen and osteopenia/osteoporosis on clinical periodontitis in postmenopausal women [J]. J Periodontol, 1999, 70(8):823-828.
[134] Civitelli R, Pilgram TK, Dotson M, et al. Alveolar and Postcranial Bone Density in Postmenopausal Women Receiving Hormone/Estrogen Replacement Therapy: a randomized, double-blind, placebo-controlled trial. [J]. Arch Intern Med, 2002, 162:1409-1415.
[135] Hildebolt CF, Pilgram TK, Dotson M, et al. Estrogen and/or calcium plus vitamin D increase mandibular bone mass [J]. J Periodontol, 2004, 75(6):811-816.
[136] Shu L, Guan SM, Fu SM, et al. Estrogen modulates cytokine expression in human periodontal ligament cells [J]. J Dent Res, 2008, 87(2): 142-147.
[137] Liang L, Yu JF, Wang Y, Ding Y. Estrogen regulates expression of osteoprotegerin and RANKL in human periodontal ligament cells through estrogen receptor beta [J]. J Periodontol, 2008, 79(9):1745-1751.
[138] Janknecht R. Regulation of the c-fos promoter [J]. Immunobiology, 1995, 193(2-4):137-142.
[139] Wagner EF. Functions of AP1 (Fos/Jun) in bone development [J]. Ann Rheum Dis, 2002, 61:ii40-2.
[140] McCabe LR, Kockx M, Lian J, et al. Selective expression of fos-and jun- related genes during osteoblast proliferation and differentiation [J]. Exp Cell Res. 1995, 218(1): 255-262.
[141] Pearman AT, Chou WY, Bergman KD, et al. Parathyroid hormone induces c-fos promoter activity in osteoblastic cells through phosphorylated cAMP response element (CRE)-binding protein binding to the major CRE [J]. J Biol Chem 1996, 271(41): 25715-25721.
[142] Machwate M, Jullienne A, Moukhtar M, et al. c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-beta in osteoblastic cells [J]. Mol Endocrinol. 1995, 9(2): 187-198.
[143] Merriman HL, La Tour D, Linkhart TA, et al. Insulin-like growth factor-I and insulin-like growth factor-II induce c-fos in mouse osteoblastic cells [J]. Calcif Tissue Int, 1990, 46(4): 258-262.
[144] McCabe LR, Banerjee C, Kundu R, et al. Developmental expression and activities of specific fos and jun proteins are functionally related to osteoblast maturation: role of Fra- 2 and Jun D during differentiation [J]. Endocrinology, 1996, 137(10): 4398-4408.
[145] Palcy S,Bolivar, I, Goltzman D. Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor betal and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells [J]. J Bone Miner Res. 2000, 15(12): 2352-2361.
[146] Closs EI, Murray AB, Schmidt J, et al. c-fos expression precedes osteogenic differentiation of cartilage cells in vitro [J]. J Cell Biol, 1990, 111(3): 1313-1323.
[147] Wang ZQ, Ovitt C, Grigoriadis AE, et al. Bone and haematopoietic defects in mice lacking c-fos [J]. Nature, 1992, 360(6406): 741-745.
[148] Yamaguchi N, Chiba M, Mitani H. The induction of c-fos mRNA expression by mechanical stress in human periodontal ligament cells [J]. Archives of Oral Biology , 2002, 47: 465–471.
[149] Li YL, Dai ZJ, Zheng SP, et al. Individual function difference of Runx2 isoforms in bone formation by RNA inference [J]. Cell Biology International, 2008, 32 (3):S22.
[150] Ikeda R, Yoshida K, Tsukahara S, et al. The promyelotic leukemia zinc finger promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1 [J]. J Biol Chem, 2005, 280(9): 8523-8530.
[151] Ziros PG, Gil AP, Georgakopoulos T, et al. The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells [J]. J Biol Chem. 2002, 277(26):23934-23941.
[152] Qi H, Aguiar DJ, Williams SM, et al. Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells [J]. Proc Natl Acad Sci U S A, 2003, 100(6):3305-3310.
[2]邵敬於。性激素的临床应用,复旦大学出版社.
[3]丰有占,沈铿。妇产科学人民卫生出版社.
[4] Yen. SS: The Human Menstrual Cycle: Neuroendocrine Regulation. Reproductive Endocrinology, 1991a, 3rd edition, 276.
[5] Mariotti A. Sex steroid hormones and cell dynamics in the periodontium. Crit Rev Oral Biol Med [J]. 1994, 5(1):27-53.
[6] Evans RM. The steroid and thyroid hormone receptors superfamily [J]. Science, 1988, 240:889-895.
[7] Wei LL, Sheridan PL, Krett NL, et al. Immunologic analysis of human breast cancer progesterone receptors. 2. Structure, phosphorylation, and processing [J]. Biochemistry, 1987, 26(19): 6262-6272.
[8] Wei LL and Horwitz KB. The structure of progesterone receptors [J]. Steroids, 1985, 46(2-3):677-695.
[9] Tung L, Mohamed MK: Hoefiler JP et al. Antagonist-occupied human progesterone Breceptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors [J]. Mol. EndocrinoL, 1993, 7(10): 1256-1265.
[10] Vegeto E, Shahbaz MM, Wen DX, et al. Human progesterone receptor A form is a cell-and promoter-specific repressor of human progesterone receptor B function [J]. Mol. Endocrinol, 1993, 7(10): 1244-1255.
[11] Wen DX, Xu YF, Mais DE, et al. The A and B isoforms of the humanprogesterone receptor operate through distinct signaling pathways within target cells [J ]. MoL Cell. Biol. 1994, 14(12): 8356-8364.
[12] Wei LL, Norris BM, Baker CJ. An N-terminally truncated third progesterone receptor protein, PR(C), forms heterodimers with PR(B) but interferes in PR(B)-DNA binding [J]. J Steroid Biochem Mol Biol. 1997, 62(4):287-297.
[13] Perrot-Applanat M, Logeat F, Groyer-Picard MT, et al. Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies [J ]. Endocrinology, 1985, 116(4):1473-1484.
[14] Duffy DM, Stouffer RL.Progesterone receptor messenger ribonucleic acid in the primate corpus luteum during the menstrual cycle: possible regulation by progesterone [J]. Endocrinology, 1995,136(5):1869-1876.
[15] Batra S, Iosif S. Progesterone receptors in human vaginal tissue [J]. Am J Obstet Gynecol, 1985, 153(5):524-528.
[16] Terner C. Progesterone and progestins in the male reproductive system [J]. Ann N Y Acad Sci. 1977, 286:313-320.
[17] Perrot-Applanat M, Groyer-Picard MT, Lorenzo F, et al. Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors [J]. Cancer Res, 1987, 47(10):2652-2661.
[18] Perrot-Applanat M, Cohen-Solal K, Milgrom E, et al. Progesterone receptors expression in human saphenous veins [J]. Circulation, 1995(10), 92:2975-2983.
[19] Kawahara K, Shimazu A. Expression and intracellular localization of progesterone receptors in cultured human gingival fibroblasts [J]. J Periodontal Res, 2003, 38(3):242-246.
[20] MacNamara P, O'Shaughnessy C, Manduca P, et al. Progesteronereceptors are expressed in Human osteoblast-like cell lines and in primary human osteoblast cultures [J]. Calcif Tissue Int, 1995, 57(6):436-441.
[21] Gorski J, Toft D, Shyamala G, et al. Hormone Receptors: Studies on the Interaction of Estrogen with the Uterous [J]. Recent Prog. Horm. Res, 1968, 24:45-80.
[22] Jensen EV, Suzuki T, Kawashima T, et al. A Two-Step Mechanism for the Interaction of Estradiol with Rat Uterous [J]. Proc. Natl. Acad. Sci. U.S.A, 1968, 59:632-638.
[23] Dijkema R,Sehoonen WG,Teuwen R,et al. Human progesterone receptor A and B isoforms in CHO cells. I. Stable transfection of receptor and receptor-responsive reporter genes: transcription modulation by (anti)progestagens [J]. J Steroid Biochem Mol Biol, 1998, 64(3-4): 147-156.
[24] Kumar NS,Richer J,Owen G,et al. Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action [J]. Cancer Res,1998,58(9):1860-1865.
[25] Rickard D, Harris SA, Turner R, et al. Estrogen and Progesterone [M] .Principles of Bone Biology, second edition, 668.
[26] Clark JH, Schrader WT, O'Malley BW: Mechanism of Action of Steroid Hormones [M]. Williams Textbook of Endocrinology, 1992, 8th edition, 36.
[27] Evans RM. The steroid and thyroid hormone receptor superfamily [J].Science 240 1988, 240: 889-895.
[28] Tsai MJ, O'Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members [J]. Annu Rev Biochem, 1994, 63: 451-486.
[29] Bramley T. Non-genomic progesterone receptors in the mammalian ovary:some unresolved issues [J]. Reproduction 2003, 125(1):3–15.
[30] Gerdes D, Christ M, Haseroth K, et al. Nongenomic actions of steroids-from laboratory to clinical implications [J].J Paediatr Endocrinol Metab, 2000, 13(7):853–878.
[31] Grosse B, Kachkache M, Le Mellay V, et al. Membrane signalling and progesterone in female and male osteoblasts. I. Involvement of intracellular Ca2+, inositol trisphosphate, and diacylglycerol, but not cAMP [J]. J Cell Biochem, 2000, 79(2):334-345.
[32] Boonyaratanakornkit V, Scott MP, Ribon V, et al. Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases [J]. Mol Cell, 2001, 8(2):269-280.
[33] Anonymous. Osteoporosis prevention, diagnosis and therapy. NIH Consens Statement, 2000, 17: 1 - 45.
[34] Riggs BL. Overview of osteoporosis [J]. West J Med. 1991, 154(1): 63–77.
[35] Payne JB, Reinhardt RA, Nummikoski PV. Longitudinal alveolar bone loss in postmenopausal osteoprorotic/osteopenic women [J]. Osteoporos Int, 1999, 10(1):34-40.
[36] Wells G, Cranney A, Peterson J, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women [J]. Cochrane Database Syst Rev. 2008 Jan 23, (1):CD004523.
[37] McCabe LR, Last TJ , Lynch M, et al. Expression of cell growth and bone phenotypic genes during the cell cycle of normal diploid osteoblasts and osteo sarcoma cells [J]. J Cell Biochem, 1994, 56(2): 274-282.
[38] Zheng MH, Wood DJ, Papadimitriou JM. What′s new in the role of cytokines on osteoblast proliferation and differentiation [J]. Pathol Res Pract, 1992, 188(8): 1104-1121.
[39] Owen TA, Aronow M, Shalhoub V, et al. Progressive development of the rat o steoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix [J]. J Cell Physiol, 1990, 143(3): 420-430.
[40] Lerner UH. Bone remodeling in post-menopausal osteoporosis [J]. J Dent Res, 2006, 85(7):584-595.
[41] Albright F, Smith PH, and Richardson AM. Post-menopausal osteoporosis: Its clinical features. J Am Med Assos, 1941, 116:2465-2474.
[42] Burnett, CC, and Reddi AH. Influence of estrogen and progesterone on matrix-induced endochondral bone formation [J]. Calcif Tissue Int, 1983, 35(4-5):609-614.
[43] Snow, GR, and Anderson C. The effects of continuous progesterone treatment on cortical bone remodeling activity in beagles [J]. Calcif Tissue Int. 1985, 37(3): 282- 286.
[44] Barengolts EI, Gajardo HF, Rosol TJ, et al. Effects of progesterone on postovariectomy bone loss in aged rats [J]. J Bone Miner Res, 1990, 5(11):1143-1147.
[45] Barengolts, EI, Kouznetsova T, Segalene A, et al. Effects of progesterone on serum levels of IGF-1 and on femur IGF-1 mRNA in ovariectomized rats [J]. J Bone Miner Res, 1996, 11(10): 1406-1412.
[46] Prior JC, Vigna YM, Barr SI, et al. Cyclic medroxyprogesterone treatment increases bone density: A controlled trial in active women with menstrual cycle disturbances [J]. Am J Med, 1994, 96(6): 521-530.
[47] McNeeley SG Jr, Schinfeld JS, Stovall TG, et al. Prevention of osteoporosis by medroxyprogesterone acetate in postmenopausal women [J]. Int J Gynaecol Obstet, 1991, 34(3):253-256.
[48] Grey A, Cundy T, Evans M, et al. Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post- menopausal women [J]. Clin. Endocrinol. 1996, 44(3): 293-296.
[49] Gallagher JC, Kable WT, Goldgar D. Effect of progestin therapy on cortical and trabecular bone: Comparison with estrogen [J]. Am J Med, 1991, 90(2): 171-178.
[50] Grecu EO, Weinshelbaum A, Simmons R. Effective therapy of glucocorticoid-induced osteoporosis with methoxyprogesterone acetate [J]. Calcif Tissue Int, 1990, 46(5):294-299.
[51] Gbolade B, Ellis S, Murby B, et al. Bone density in long term users of depot medroxyprogesterone acetate [J]. Br J Obstet Gynaecol. 1998, 105(7): 790-794.
[52] Parfitt AM. What is the normal rate of bone remodeling? [J]. Bone, 2004, 35(1):1-3.
[53] Boivin G, Anthoine-Terrier C, Morel G. Ultrastructural localization of endogenous hormones and receptors in bone tissue: an immunocytological approach in frozen samples [J]. Micron. 1994, 25(1):15-27.
[54] Tremollieres FA, Strong DD, Baylink DJ, et al. Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production [J]. Acta Endocrinol, 1992, 126(4): 329-337.
[55]梁敏.孕酮和18-甲左炔诺孕酮对成骨细胞作用机制的研究.中南大学博士学位论文.
[56] Verharr HJ, Damen CA, Duursma SA, et al. A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro. Bone, 1994, 15(3):307-311.
[57] Luo XH, Liao EY, Su X. Progesterone upregulates TGF-βisoforms (β1,β2, andβ3) expression in normal human osteoblast- like cells [J]. Calcif Tissue Int, 2002, 71(4):329-334.
[58] Girasole G, Jilka RL Passeri G, et al. 17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens [J]. J Clin Invest, 1992, 89(3): 883-891.
[59] Huang QX, Zhou HD, Liao EY, et al. Effects of estradiol and progesterone on the expression of insulin receptor substrate in human osteoblasts [J]. Zhonghua Yi Xue Za Zhi, 2005, 85(11):743-746.
[60] Luo XH, Liao EY. Progesterone differentially regulates the membrane- type matrix metalloproteinase-1 (MT1-MMP) compartment of proMMP-2 activation in MG-63 cells [J]. Horm Metab Res 2001, 33(7): 383-388.
[61] Ishida Y, Bellows CG, Tertinegg I, et al. Progesterone-mediated stimulation of osteoprogenitor proliferation and differentiation in cell populations derived from adult or fetal rat bone tissue depends on the serum component of the culture media [J]. Osteoporos Int, 1997, 7(4):323-330.
[62] Günhan M, Günhan O, Celasun B,et al. Estrogen and progesterone receptors in the peripheral giant cell granulomas of the oral cavity[J]. J Oral Sci, 1998, 40(2):57-60.
[63] Liao EY, Luo XH, Su X. Comparison of the effects of 17beta-E2 and progesterone on the expression of osteoprotegerin in normal human osteoblast-like cells [J]. J Endocrinol Invest. 2002, 25(9):785-90.
[64] Canalis E and Raisz LG. Effect of sex steroids on bone collagen synthesis in vitro [J]. Calcif Tissue Res. 1978, 25(2):105-110.
[65] Scheven BA, Damen CA, Hamilton NJ, et al. Stimulatory effects ofestrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro [J]. Biochem Biophys Res Commun, 1992, 186(1):54–60.
[66] Slootweg MC, Ederveen AG, Schot LP, et al. Oestrogen and progesterone synergistically stimulate human and rat osteoblast proliferation [J]. J Endocrinol, 1992, 133(2): R5-R8.
[67] Lu CC, Tsai SC, Wang SW, et al. Effects of ovarian steroid hormones and thyroxine on calcitonin secretion in pregnant rats [J]. Am J Physiol, 1998, 274(2 Pt 1):E246-252.
[68] Jeffcoate W. Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency [J] .Ann Clin Biochem, 1999, 36(Pt2):151-157.
[69] Nelson HD, Humphrey LL, Nygren P, et al. Postmenopausal hormone replacement therapy: scientific review. JAMA, 2002, 288(7):872-881.
[70] Yamamoto Y, Kurabayashi T, Tojo Y, et al. Effects of progestins on the metabolism of cancellous bone in aged oophorectomized rats [J]. Bone, 1998, 22(5):533-537.
[71] Ishida Y and Heersche JN. Progesterone- and dexamethasone-dependent osteoprogenitors in bone cell populations derived from rat vertebrae are different and distinct [J]. Endocrinology, 1999, 140(7): 3210-3218.
[72] Gunnet JW, Granger K, Cryan E, et al. Characterization of the progestin receptors in the human TE85 and murine MC3T3-E1 osteoblast-like cell lines [J].J Endocrinol, 1999, 163(1):139-147.
[73] Eriksen EF, Colvard DS, Berg NJ, et al. Evidence of estrogen receptors in normal human osteoblast-like cells [J]. Science, 1988, 241(4861): 84-86.
[74] Harris SA, Tau KR, Enger RJ, et al. Estrogen response in the hFOB 1.19 human fetal osteoblastic cell line stably transfected with the humanestrogen receptor gene [J]. J Cell Biochem, 1995, 59(2), 193- 201.
[75] Mac Namara P and Loughrey HC. Progesterone receptor A and B isoforms in human osteoblasts [J]. Calcif Tissue Int, 1998, 63(1): 39-46.
[76] Schmidt IU, Wakley GK, Turner RT. Effects of estrogen and progesterone on tibia histomorphometry in growing rats [J]. Calcif Tissue Int, 2000, 67(1):47-52.
[77] Delaveyne-Bitbol R, Garabedian M. In vitro responses to 17beta-estradiol throughout pubertal maturation in female human bone cells [J]. J Bone Miner Res, 1999, 14(3):376-385.
[78] Mizunuma H, Okano H, Soda M, et al. Prevention of postmenopausal bone loss with minimal uterine bleeding using low dose continuous estrogen/ progestin therapy: a 2-year prospective study [J] .Maturitas, 1997, 27(1): 69-76.
[79] Jeffcoat MK. Bone loss in the oral cavity [J]. J Bone Min Res, 1993, 8 suppl: S467-473.
[80] Streckfus CF , Johnson RB , Nick T, et al . Comparison of alverolar bone loss, alverlar bone density and second metacarpal bone dentisy, salivary and gingival crevicular fluid interleukin-6 concentrations in healthy premenopausal and postmenopausal women on estrogen therapy [J]. J Gerontol Biol A Sci Med Sci, 1997, 52(6): M343-351.
[81] Elovic RP, Hipp JA, Hayes WC. Maxillary molar extraction causes increased bone loss in the mandible of ovariectomized rats [J]. J bone Miner Res, 1995, 10 (7):1087-1093.
[82] Bollen AM, Taguchi A, Hujoel PP, et al. Case-control study on self- reported osteoporotic fractures and mandibular cortical bone [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000, 90(4): 518-524.
[83] Tezal M, Wactawski-Wende J , Grossi SG, et al . The relationship between bone mineral density and periodontitis in postmenopausal women. J Periodontol, 2000, 71(9):1492-1498.
[84] Dumitrescu AL. Occurrence of self-reported systemic medical conditions in patients with periodontal disease [J]. Rom J Intern Med, 2006, 44(1): 35-48.
[85] Otogoto J, Ota N. Correlation between periodontal disease and osteoporosis using panoramic radiographic parameters for diagnosed osteoporosis in dental clinic [J]. Clin Calcium, 2003, 13(5): 582-586.
[86] Famili P, Cauley J, Suzuki JB, et al. Longitudinal study of periodontal disease and edentulism with rates of bone loss in older women. J Periodontol, 2005, 76(1):11-15.
[87] Pilgram TK, Hildebolt CF, Dotson M, et al. Relationships between clinical attachment level and spine and hip bone mineral density: data from healthy postmenopausal women [J]. J Periodontol, 2002, 73(3): 298-301.
[88]张铭.妊娠期大鼠正畸力刺激下牙周组织中雌、孕激素受体表达变化的实验研究.四川大学口腔医学博士专业论文.
[89] Tilakaratne A, Soory M, Ranasinghe AW,et al. Periodontal disease status during pregnancy and 3 months post-partum, in a rural population of Sri-Lankan women[J]. J Clin Periodontol, 2000, 27(10):787-792.
[90] Kornman KS, Loesche WJ. The subgingival microbial flora during pregnancy [J]. J Periodontal Res, 1980, 15(2):111-122.
[91] Tsai CC, Chen KS. A study on sex hormones in gingival crevicular fluid and black pigmented bacteria in subgingival plaque of pregnant women [J]. Gaoxiong Yi Xue Ke Xue Za Zhi, 1995, 11(5):265-273.
[92] Lapp CA,Lohse JE,Lewis JB, et al. The effects of progesterone on matrixmetalloproteinases in cultured human gingival fibroblasts [J]. J Periodontol, 2003, 74(3):277-288.
[93] Hellsing E, Hammarstr?m L. The effects of pregnancy and fluoride on orthodontic tooth movements in rats [J]. Eur J Orthod, 1991, 13(3):223-230.
[94] Gould TR, Melcher AH, Brunette DM. Migration and division of progenitor cell populations in periodontal ligament after wounding [J]. J Periodont Res, 1980, 15(1):20-42.
[95] Morishita M, Yamamura T, Bachchu MA, et al. The effects of oestrogen on osteocalcin production by human periodontal ligament cells [J]. Arch Oral Biol, 1998, 43(4):329-333.
[96] Nojima N, Kobayashi M, Shionome M, et al. Fibroblastic cells derived from bovine periodontal ligaments have the phenotypes of osteoblasts [J]. J Periodontal Res, 1990, 25(3):179-185.
[97] Somerman MJ,Archer SY,Imm GR. Comparative study of human periodontal ligament cells and gingival fibroblasts in vitro [J]. J Dent Res, 1988, 67(1):66-70.
[98] Guiochon-Mantel A,Lescop P,Christin-Maitre S, et al. Nucleocytoplasmic shuttling of the progesterone receptor [J]. EMBO J, 1991, 10(12): 3851- 3859.
[99] J?nsson D, Wahlin ?, Idvall I, et al. Differential effects of estrogen on DNA synthesis in human periodontal ligament and breast cancer cells [J]. J Periodontal Res, 2005, 40(5): 401-406.
[100] Amar S, Chung KM. Clinical implications of cellular biologic advances in periodontal regeneration [J] .Curr Opin Periodontol,1994,18(2):128-140.
[101] Ishida Y, Heersche JN. Progesterone stimulates proliferation anddifferentiation of osteoprogenitor cells in bone cell populations derived from adult female but not from adult male rats [J]. Bone, 1997, 20(1):17-25.
[102]陈璐璐,Scholler J,Fpged NT.孕酮对离体胎鼠头盖骨成骨细胞增殖与分化的影响[J].中华妇产科杂志,1997,32(9):538-540.
[103] Lekic P, Rojas J, Birek C, et al. Phenotypic comparison of periodontal ligament cells in vivo and in vitro[J]. J Periodontal Res, 2001, 36(2):71-79.
[104] Lekic P,McCulloch CA. Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue [J]. Anat Rec.1996, 245(2):327-341.
[105] Shimizu Y, Inomata Y, Tagami A. Suppression of osteoclast-like cell formation by periodontal ligament cells [J]. J Bone Miner Metab, 1996, 14:65-72.
[106] Arceo N, Sauk JJ, Moehring J, et al. Human periodontal cells initiate mineral-like nodules in vitro[J]. J Periodontol, 1991, 62(8):499-503.
[107] Lang H, Schuler N, Arnhold S, et al. Formation of differentiated tissues in vivo by periodontal cell populations cultured in vitro [J]. J Dent Res, 1995, 74(5):1219-1225.
[108] Lindskog S, Bloml L. Quality of periodontal healing. IV: enzyme histochemical evidence for an osteoblast origin of reparative cementum [J]. Swed Dent J, 1994, 18(5): 181-189.
[109] Mukai M, Yoshimine Y, Akamine A, et al. Bone-like nodules formed in vitro by rat periodontal ligament cells [J]. Cell Tissue Res, 1993, 271(3): 453-460.
[110] Morishita M, Yamamura T, Shimazu A, et al. Estradiol enhances theproduction of mineralized nodules by human periodontal ligament cells [J]. J Clin Periodontol, 1999, 26(11):748-751.
[111] Quarles LD, Yohay DA, Lever LW,et al. Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development [J]. J Bone Miner Res, 1992, 7(6): 683-692.
[112] Pavlin D, Dove SB, Zadro R,et al. Mechanical loading stimulates differentiation of periodontal osteoblasts in a mouse osteoinduction model: effect on type I collagen and alkaline phosphatase genes [J]. Calcif Tissue Int, 2000, 67(2):163-172.
[113] Goseki M, Oida S, Takeda K, et al. Identification of bone-type alkaline phosphatase mRNA from human periodontal ligament cells [J]. J Dent Res, 1995, 74(1):319–322.
[114] Groeneveld MC, Everts V, Beertsen W. Alkaline phosphatase activity in the periodontal ligament and gingiva of the rat molar: its relation to cementum formation [J]. J Dent Res, 1995, 74(7):1374–1381.
[115] Ogata Y, Niisato N, Sakurai T,et al. Comparison of characteristics of human gingival fibroblasts and periodontal ligament cells [J]. J Periodontol, 1995, 66(12):1025-1031.
[116] Murakami Y, Kojima T, Nagasawa T,et al. Novel isolation of alkaline phosphatase-positive subpopulation from periodontal ligament fibroblasts [J]. J Periodontol, 2003, 74(6): 780-786.
[117] Isaka J, Ohazama A, Kobayashi M, et al. Participation of periodontal ligament cells with regeneration of alveolar bone [J]. J Periodontol, 2001, 72(3): 314-323.
[118] Bellahcène A, Antoine N, Clausse N, et al. Detection of bone sialoproteinin human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels [J]. Lab Invest, 1996, 75(2):203-210.
[119] Chen J, Shapiro H, Sodek J. Development expression of bone sialoprotein mRNA in rat mineralized connective tissues [J]. J Bone Miner Res, 1992, 7(8):987-997.
[120] Kobayashi D, Takita H, Mizuno M, et al. Time-dependent expression of bone sialoprotein fragments in osteogenesis induced by bone morphogenetic protein [J]. J Biochem. 1996, 119(3):475-481.
[121] Cho P, Schneider GB, Krizan K, et al. Examination of the bone-implant interface in experimentally induced osteoporotic bone [J]. Implant Dent, 2004, 13(1):79-87.
[122] Chien HH, Lin WL, Cho MI. Expression of TGF-beta isoforms and their receptors during mineralized nodule formation by rat periodontal ligament cells in vitro [J]. J Periodontal Res. 1999, 34(6):301-309.
[123] Lekic P, Sodek J, McCulloch CA. Osteopontin and bone sialoprotein expression in regenerating rat periodontal ligament and alveolar bone [J]. Anat Rec. 1996, 244(1):50-58.
[124] Domon S, Shimokawa H, Yamaguchi S, et al. Temporal and spatial mRNA expression of bone sialoprotein and type I collagen during rodent tooth movement [J]. Eur J Orthod, 2001, 23(4):339-348.
[125] Hauschka PV. Osteocalcin: the vitamin K-dependent Ca2+- binding protein of bone matrix [J]. Haemostasis, 1986, 16(3-4):258–272.
[126] Liang L, Yu JF, Wang Y, Wang G, Ding Y. Effect of estrogen receptor beta on the osteoblastic differentiation function of human periodontal ligament cells [J]. Arch Oral Biol, 2008, 53(6):553-557.
[127] Goldsmith HL, Labrosse JM, Mclntosh FA, et al. Homotypic interactionsof soluble and immobilized osteopontin [J]. Ann Biomed Eng, 2002, 30(6):840-850.
[128] Noda M, Tsuji K, Nifuji A. Osteopontin: a topic from the point of bone morphology [J]. Clin Calcium, 2003, 13(4):464-466.
[129] Wan YM, Ma YJ, Zhang XY, et al. Effects of rotation on osteonectin and osteopontin mRNA level of cultured osteoblasts in rats. Sheng Li Xue Bao, 2005, 57(3):384-388.
[130] Johnson GA, Spencer TE, Burghardt RC, et al. Progesterone modulation of osteopontin gene expression in the ovine uterus [J]. Biol Reprod, 2000, 62(5):1315-1321.
[131] Lin DG, Kenny DJ, Barrett EJ. Storage conditions of avulsed teeth affect the phenotype of cultured human periodontal ligament cells [J]. J Periodontal Res, 2000, 35(1):42-50.
[132] Wactawski-Wende J, Hausmann E, Hovey K, et al. The association between osteoporosis and alveolar crestal height in postmenopausal women [J]. J Periodontol, 2005, 76(11 Suppl):2116-2124.
[133] Reinhardt RA, Payne JB, Maze CA. Influence of estrogen and osteopenia/osteoporosis on clinical periodontitis in postmenopausal women [J]. J Periodontol, 1999, 70(8):823-828.
[134] Civitelli R, Pilgram TK, Dotson M, et al. Alveolar and Postcranial Bone Density in Postmenopausal Women Receiving Hormone/Estrogen Replacement Therapy: a randomized, double-blind, placebo-controlled trial. [J]. Arch Intern Med, 2002, 162:1409-1415.
[135] Hildebolt CF, Pilgram TK, Dotson M, et al. Estrogen and/or calcium plus vitamin D increase mandibular bone mass [J]. J Periodontol, 2004, 75(6):811-816.
[136] Shu L, Guan SM, Fu SM, et al. Estrogen modulates cytokine expression in human periodontal ligament cells [J]. J Dent Res, 2008, 87(2): 142-147.
[137] Liang L, Yu JF, Wang Y, Ding Y. Estrogen regulates expression of osteoprotegerin and RANKL in human periodontal ligament cells through estrogen receptor beta [J]. J Periodontol, 2008, 79(9):1745-1751.
[138] Janknecht R. Regulation of the c-fos promoter [J]. Immunobiology, 1995, 193(2-4):137-142.
[139] Wagner EF. Functions of AP1 (Fos/Jun) in bone development [J]. Ann Rheum Dis, 2002, 61:ii40-2.
[140] McCabe LR, Kockx M, Lian J, et al. Selective expression of fos-and jun- related genes during osteoblast proliferation and differentiation [J]. Exp Cell Res. 1995, 218(1): 255-262.
[141] Pearman AT, Chou WY, Bergman KD, et al. Parathyroid hormone induces c-fos promoter activity in osteoblastic cells through phosphorylated cAMP response element (CRE)-binding protein binding to the major CRE [J]. J Biol Chem 1996, 271(41): 25715-25721.
[142] Machwate M, Jullienne A, Moukhtar M, et al. c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-beta in osteoblastic cells [J]. Mol Endocrinol. 1995, 9(2): 187-198.
[143] Merriman HL, La Tour D, Linkhart TA, et al. Insulin-like growth factor-I and insulin-like growth factor-II induce c-fos in mouse osteoblastic cells [J]. Calcif Tissue Int, 1990, 46(4): 258-262.
[144] McCabe LR, Banerjee C, Kundu R, et al. Developmental expression and activities of specific fos and jun proteins are functionally related to osteoblast maturation: role of Fra- 2 and Jun D during differentiation [J]. Endocrinology, 1996, 137(10): 4398-4408.
[145] Palcy S,Bolivar, I, Goltzman D. Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor betal and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells [J]. J Bone Miner Res. 2000, 15(12): 2352-2361.
[146] Closs EI, Murray AB, Schmidt J, et al. c-fos expression precedes osteogenic differentiation of cartilage cells in vitro [J]. J Cell Biol, 1990, 111(3): 1313-1323.
[147] Wang ZQ, Ovitt C, Grigoriadis AE, et al. Bone and haematopoietic defects in mice lacking c-fos [J]. Nature, 1992, 360(6406): 741-745.
[148] Yamaguchi N, Chiba M, Mitani H. The induction of c-fos mRNA expression by mechanical stress in human periodontal ligament cells [J]. Archives of Oral Biology , 2002, 47: 465–471.
[149] Li YL, Dai ZJ, Zheng SP, et al. Individual function difference of Runx2 isoforms in bone formation by RNA inference [J]. Cell Biology International, 2008, 32 (3):S22.
[150] Ikeda R, Yoshida K, Tsukahara S, et al. The promyelotic leukemia zinc finger promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1 [J]. J Biol Chem, 2005, 280(9): 8523-8530.
[151] Ziros PG, Gil AP, Georgakopoulos T, et al. The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells [J]. J Biol Chem. 2002, 277(26):23934-23941.
[152] Qi H, Aguiar DJ, Williams SM, et al. Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells [J]. Proc Natl Acad Sci U S A, 2003, 100(6):3305-3310.