摘要
目的 从骨髓微环境角度研究甲状旁腺激素 (parathyroidhormone,PTH)对老年大鼠骨形成刺激作用的分子机制。方法 8只 2 0月龄雄性大鼠随机平均分两组 ,每组 4只 ,分别给予人重组甲状旁腺激素和生理盐水 ,1次 /天 ,5次 /周 ,8周后处死 ,无菌获取股骨和腰椎骨髓细胞 ,用RT PCR法检测成骨功能相关基因核结合因子α1(Cbfα1)、碱性磷酸酶 (ALP)和骨钙素 (BGP)及破骨细胞分化成熟调节基因NF κB受体激活因子配体(RANKL)、骨保护素 (OPG)、巨噬细胞克隆刺激因子 (M CSF)、肿瘤坏死因子受体相关因子 6 (TRAF6 )和白介素 - 6 (IL 6 )mRNA表达水平。结果 PTH显著增加骨髓细胞中成骨功能相关基因Cbfα1、ALP和BGPmRNA表达 (P <0 .0 5～ 0 .0 0 1) ;调整破骨细胞分化成熟调节基因mRNA表达 :下调RANKL、M CSF和TRAF6mRNA表达 (P <0 .0 5～ 0 .0 1) ,上调OPGmRNA表达 (P <0 .0 1)和IL 6mRNA表达 (P <0 .0 5 )。股骨与腰椎呈类似变化。结论 PTH增加老年大鼠骨量可能与其强烈刺激骨髓微环境中成骨活性基因表达 ,同时调整破骨细胞分化和功能成熟状态有关。
Purpose To investigate the molecular mechanism of parathyroid hormone (PTH) enhancing bone formation at the level of bone marrow microenvironment. Methods Twenty monthold 8 rats divided into 2 groups were randomly assigned to receive either subcutaneous doses of recombinant human parathyroid hormone (rhPTH) or normal saline (NS),5 times/week.After 8 weeks,bone marrow cells (BMC) were collected from femur and lumbar vertebra.Semi-quantity RT-PCR was used to analysed the mRNA expression of alkaline phosphatase (ALP),bone Gla-containing protein (BGP),core binding factor alpha 1 (Cbfα1) which relates to bone forming,receptor activator of NF-κB ligand (RANKL),osteoprotegerin(OPG),macrophage colony stimulating factor(M-CSF)、tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin(IL-6) which relates to osteoclast differentiation and maturation. Results PTH significantly increased mRNA expression of Cbfα1、ALP and BGP that relates to bone forming in BMC(P<0.05- 0.001);PTH regulated mRNA expression of genes relates to osteoclast differentiation and maturation:RANKL、M-CSF and TRAF6 mRNA were down-regulated in PTH group(P<0.05-0.01),OPG and IL-6 mRNA were up-regulated (P<0.01 and P<0.05 respectively).Similar changes of mRNA expression of the above genes existed both in femur BMC and in lumbar vertebra BMC. Conclusions PTH increasing old rats' bone mass may be related to its dramatically enhancing the expression of genes related to bone for-ming as well as regulating the expression of genes related to osteoclast differentiation and maturation in bone marrow microenvironment.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2005年第2期219-221,242,共4页
Hehai University Journal of Medical Sciences
基金
国家自然科学基金资助项目 (3 0 170 43 9)
