绝经女性骨组织中瘦素对骨代谢指标的影响及相关机制研究  

Effect and mechanism of leptin on bone metabolism in postmenopausal women

作　　者：陈志强[1] 邹云雯[2] 闫军[1] 

机构地区：[1]山东省聊城市人民医院骨外科,252000 [2]青岛大学医学院附属医院骨科

出　　处：《中华骨科杂志》2015年第10期997-1003,共7页Chinese Journal of Orthopaedics

基　　金：山东省自然基金项目（ZR2014HP38）

摘　　要：目的探讨瘦素对绝经后骨质疏松妇女骨代谢指标的影响及相关机制。方法回顾性分析2008年1月至2014年1月，40例绝经后骨质疏松女性患者[骨质疏松组，年龄（69．29±12．84）岁，体重指数平均（23．32±1．19）kg/m2，脂肪量平均（19．93±2．66）kg]和42例无骨质疏松绝经后妇女[骨质正常组，年龄（72．55±14．21）岁，体重指数平均（24．11±1．31）kg／m2，脂肪量平均（17．89±3．18）kg]资料，采用免疫细胞化学方法检测成骨细胞内瘦素受体的表达情况，而后再分别施加1×10ng／ml、1×10^2ng／ml、1×10^3ng／ml、1×10^4ng/ml浓度的瘦素，在24h、48h、96h时间点观察成骨细胞增殖、分化和矿化改变。检测瘦素作用骨髓间质干细胞（bone marrow mesenchymal stemcells，BMSCs）源性定向分化后成骨及成脂基因的表达变化。结果骨质正常组和骨质疏松组患者的成骨细胞膜及胞浆内均有瘦素受体的分布。骨质疏松组中不同浓度瘦素均促进成骨细胞的增殖，分化以及矿化，1×10ng／ml、1×10^2ng／ml、1×10^3ng／ml浓度的瘦素作用下成骨细胞MTT增长率及碱性磷酸酶浓度测定结果均明显增加，其中1×10^2ng／ml浓度的作用最强，且具有时间依赖性，在96h以内成骨细胞增长率逐渐递增，在3周内细胞分泌碱性磷酸酶浓度逐渐升高。基因结果分析显示，BMSCs定向分化经1×10^2ng／ml瘦素处理后核因子κB受体活化因子配体／骨保护素的水平均显著增加。结论瘦素受体存在于成骨细胞中。BMSCs定向分化经瘦素刺激后促进成骨抑制成脂分化，抑制骨吸收。Objective To investigate the effects of Leptin on the base of anthropometry, densitometry, and biochemistry and reveal the role of Leptin in bone metabolism in postmenopausal women with osteoporosis （OP）. Methods From January 2008 to January 2014, data of 82 postmenopausal females with or without OP were analyzed. They were randomized into two groups： OP （n=40） and conditional control group （CON） （n=42）. The expression of Leptin receptors in osteoblasts was observed by immunohis- tochemistry. 1 × 10 ng/ml, 1 × 10^2 ng/ml, 1× 10^3 ng/ml, 1 × 10^4 ng/ml of Leptin were added respectively. Then the proliferation, differ- entiation and mineralization of osteoblasts were measure at 24 h, 48 h and 96 h. The gene expressions of bone marrow mesenchy- real stem cells （BMSCs） derived osteoblasts and adipocytes treated with Leptin were examined by quantitative analysis of Real time-PCR. Results The expression of Leptin receptors in osteoblasts was observed on plasma membranes and cytoplasm in the normal group and osteoporosis group. In osteoporosis group, different concentrations of Leptin enhanced cell proliferation, cell dif- ferentiation and cell mineralization. The growth rate of MTT and the concentration of ALP in the serum of were significantly in- creased with the effects of 1 × 10 ng/ml, 1× 10^2 ng/ml and 1 × 10^3 ng/ml of Leptin, and the action of 1 × 10^2 ng/ml Leptin was the most powerful with time dependence. Within 96 hours, the growth rate of osteoblasts increased gradually, and the concentration of ALP increased gradually in 3 weeks. The expression of RANKL/OPG in bone marrow BMSCs derived osteoblasts treated with Leptin were significantly increased. Conclusion Leptin receptor is present in osteoblasts, and Leptin affects biological behaviors of os- teoblasts through receptors. The direct effect of Leptin may relate the expression of RANKL/OPG. Then, the balance between bone resorption and bone formation was broken and finally osteoporosis occurred. Lepin may promote osteogenesis

关 键 词：骨质疏松 绝经后 瘦素 骨疾病 代谢性 

分 类 号：R580[医药卫生—内分泌]