雄激素和雄激素受体对骨代谢的调控及机制研究进展  

Progress in the Effects of Androgen and Androgen Receptor on Bone Metabolism and Its Mechanisms

作　　者：付绍婷 王晓慧[1] Fu Shaoting;Wang Xiaohui(School of Kinesiology, Shanghai University of Sport, Shanghai 200438, Chin)

机构地区：[1]上海体育学院运动科学学院,上海200438

出　　处：《中国细胞生物学学报》2018年第6期1041-1048,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31271274));上海市人类运动能力开发与保障重点实验室(上海体育学院)(批准号:11DZ2261100)资助的课题~~

摘　　要：骨代谢由成骨细胞介导的骨形成和破骨细胞介导的骨吸收构成。雄激素能调控骨代谢,即促进骨形成、抑制骨吸收,在骨骼生长、骨峰值的获得和骨量维持中起重要作用;且该作用主要通过雄激素受体(androgen receptor,AR)介导。AR调控骨代谢的作用,一方面是通过直接调控骨代谢相关的AR靶基因(如与成骨相关的I型胶原蛋白α1、骨钙素、组织非特异性碱性磷酸酶、小整合素结合配体N-端连接糖蛋白和与破骨相关的核因子κB受体活化因子配体(RANKL)、组织蛋白酶K的表达;另一方面是通过间接调控骨代谢的多个信号通路[如Wnt/β-catenin、骨形态发生蛋白(BMP)/Smads-Runt相关转录因子2(Runx2)、RANKL/骨保护蛋白(OPG)、PI3K/Akt和MAPK信号通路]实现的。该文主要就雄激素/AR在骨代谢调控中的作用及机制作一综述,对丰富AR调控骨代谢的理论认识和骨代谢性疾病的药物研发具有重要意义。Bone metabolism comprises bone formation mediated by osteoblasts and bone resorption by osteoclasts. Androgen plays a vital role in regulating bone metabolism by increasing bone formation and decreasing bone resorption, and this effect is mainly mediated by androgen receptor（AR）, thus achieving the role of androgen in bone growth, peak bone mass gain, and bone mass maintenance; AR exerts its effects via several pathways, on one hand, AR directly mediates the expression of bone metabolism-related AR target genes（such as osteogenic-associated type 1 a1 collagen, osteocalcin, tissue non-specific alkaline phosphatase, small integrin-binding ligand, N-linked glycoprotein and osteoclastic-associated receptor activator of nuclear factor kappa-B ligand and cathepsin K）. On the other hand, AR＇s role in bone metabolism is achieved by indirectly modulating several signal pathways involved in bone metabolism, including Wnt/β-catenin, BMP/Smads-Runx2, RANKL/OPG, PI3 K/Akt and MAPKs pathways. This work reviewed the role of androgen/AR in regulating bone metabolism and its underlying mechanisms, which is of great significance for enriching the theoretical knowledge about the regulation of bone metabolism mediated by androgen/AR and for developing potential drugs for curing bone metabolic diseases.

关 键 词：雄激素受体 骨代谢 WNT/Β-CATENIN 骨形态发生蛋白/Smads Runt相关转录因子2 RANKL/骨保护蛋白 PI3K/Akt MAPK 

分 类 号：R580[医药卫生—内分泌]