Osterix在调控脊椎松质骨骨量中的作用
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摘要
目的观察Osterix在调控脊椎松质骨骨量的作用及机制。方法以Osterix敲除小鼠和Osterix转基因小鼠为观察对象,采用X线摄像、显微电子计算机X线断层摄影术(Micro-CT)和苏木素-伊红(HE)染色观察Osterix过表达或敲除后小鼠腰椎骨量的变化,抗酒石酸酸性磷酸酶(TRAP)染色观察破骨细胞的变化。免疫组织化学检测核因子-κB受体活化因子配体(RANKL)表达情况的变化。结果 Osterix转基因小鼠腰椎骨量没有明显变化,而X线片、Micro-CT和HE染色检测显示Osterix敲除小鼠在出生后12周脊椎密度和骨量增加;TRAP染色显示腰椎中破骨细胞数量减少;免疫组织化学染色检测显示其椎体中RANKL表达水平降低。结论 Osterix在调控脊椎松质骨骨量中起到重要作用。
Objective To observe the role of Osterix in controlling bone volume in vertebral body and to investigate the possible mechanism.Methods X-ray radiology,micro CT and HE staining were used to evaluate the change of bone volume in both Osterix knockout and transgenic mice.TRAP staining was used to assess the activity of osteoclasts and immunohistochemistry was used to examine the expression level of RANKL.Results No obvious changes were found in Osterix transgenic mice,while X-ray examination,micro CT and HE staining showed that the bone density and bone volume in the lumbar vertebral body increased significantly in OSX null mice 12weeks after birth.TRAP staining showed that the number of osteoclasts decreased in OSX null mice.IHC revealed that the expression level of RANKL was down-regualted in OSX null mice.Conclusion Osterix play an important role in controlling bone volume of vertebral body in mice.
Objective To observe the role of Osterix in controlling bone volume in vertebral body and to investigate the possible mechanism.Methods X-ray radiology,micro CT and HE staining were used to evaluate the change of bone volume in both Osterix knockout and transgenic mice.TRAP staining was used to assess the activity of osteoclasts and immunohistochemistry was used to examine the expression level of RANKL.Results No obvious changes were found in Osterix transgenic mice,while X-ray examination,micro CT and HE staining showed that the bone density and bone volume in the lumbar vertebral body increased significantly in OSX null mice 12weeks after birth.TRAP staining showed that the number of osteoclasts decreased in OSX null mice.IHC revealed that the expression level of RANKL was down-regualted in OSX null mice.Conclusion Osterix play an important role in controlling bone volume of vertebral body in mice.
引文
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[16]Dempster DW,Lambing CL,Kostenuik PJ,et al.Role of RANK ligand and denosumab,a targeted RANK ligand inhibitor,in bone health and osteoporosis:a review of preclinical and clinical data[J].Clin Ther,2012,34(3):521-536.
[17]Conaway HH,Pirhayati A,Persson E,et al.Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL,a response inhibited by monomeric glucocorticoid receptor[J].J Biol Chem,2011,286(36):31425-31436.
[2]Landete-Castillejos T,Molina-Quilez I,Estevez JA,et al.Alternative hypothesis for the origin of osteoporosis:the role of Mn[J].Front Biosci(Elite Ed),2012,4:1385-1389.
[3]Brandi ML.An overview of osteoporosis:from genetics to clinics[J].Aging Clin Exp Res,2011,23(2Suppl):3-5.
[4]Nakashima K,Zhou X,Kunkel G,et al.The novel zinc fingercontaining transcription factor osterix is required for osteoblast differentiation and bone formation[J].Cell,2002,108(1):17-29.
[5]Baek WY,de Crombrugghe B,Kim JE.Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance[J].Bone,2010,46(4):920-928.
[6]Zhou X,Zhang Z,Feng JQ,et al.Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice[J].Proc Natl Acad Sci U S A,2010,107(29):12919-12924.
[7]van den Bergh JP,van Geel TA,Geusens PP.Osteoporosis,frailty and fracture:implications for case finding and therapy[J].Nat Rev Rheumatol,2012,8(3):163-172.
[8]陈隽,李裕华,张莉萍,等.重庆地区骨质疏松症维生素D受体基因与骨密度关系的初探[J].重庆医学,2003,32(7):881-882.
[9]Davison KS,Siminoski K,Adachi JD,et al.Bone strength:the whole is greater than the sum of its parts[J].Semin Arthritis Rheum,2006,36(1):22-31.
[10]Friedman AW.Important determinants of bone strength:beyond bone mineral density[J].J Clin Rheumatol,2006,12(2):70-77.
[11]陶晖,余美春,杨会营,等.脂肪源干细胞移植对糖皮质激素性骨质疏松骨量影响的实验研究[J].南方医科大学学报,2011,31(5):817-821.
[12]罗改莹,鲁晓东.25-羟-维生素D与类风湿患者骨质疏松的相关性分析[J].国际检验医学杂志,2013,34(3):296-298.
[13]刘亦恒,张寿,张海英,等.甲基强的松龙治疗大鼠急性脊髓损伤后对骨密度及生物力学的影响[J].海南医学院学报,2010,16(7):824-826.
[14]肖登,杨霖,雷中杰,等.不同强度脉冲电磁场对去卵巢大鼠股骨骨密度的影响[J].激光杂志,2011,32(5):61-62.
[15]杨健,谭颖徽,裘松波.核因子-κB受体活化因子配体诱导大鼠骨髓破骨细胞形成的实验研究[J].重庆医学,2004,33(3):385-388.
[16]Dempster DW,Lambing CL,Kostenuik PJ,et al.Role of RANK ligand and denosumab,a targeted RANK ligand inhibitor,in bone health and osteoporosis:a review of preclinical and clinical data[J].Clin Ther,2012,34(3):521-536.
[17]Conaway HH,Pirhayati A,Persson E,et al.Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL,a response inhibited by monomeric glucocorticoid receptor[J].J Biol Chem,2011,286(36):31425-31436.