体外雌激素通过调控骨髓间充质干细胞FasL表达介导破骨细胞凋亡  

Estrogen promotes osteoclast apoptosis by inducing Fas ligand expression in bone marrow-derived mesenchymal stem cells in vitro

作　　者：邵秉一[1,2] 于洋[1,2] 帅逸[3] 戚朦[3] 廖立[3] 金岩[3] 杨德琴[1,2] 

机构地区：[1]重庆医科大学附属口腔医院牙体牙髓科,重庆400015 [2]重庆医科大学口腔疾病与生物医学重庆市重点实验室,重庆400015 [3]第四军医大学组织工程中心,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2013年第10期1020-1023,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家重点基础研究发展计划(973)(2011CB964700);重庆市医学重点学科建设经费基金《牙体牙髓病学》(2011)

摘　　要：目的探讨雌激素缺乏对骨髓间充质干细胞(BMSC)表达FasL水平下降对破骨细胞凋亡的影响。方法建立绝经后骨质疏松模型(去势组,切除双侧卵巢)。设立假手术组(sham)组、卵巢切除(OVX)组、OVX后雌激素(OVX+E2)处理组。将破骨细胞与3组分离的BMSC共培养,观察破骨细胞数量的改变;用annexinⅤ-FITC/7-氨基放线菌素D(7-AAD)标记,流式细胞术检测各组破骨细胞凋亡的差异;Western blot法检测OVX组与sham组及OVX+E2组BMSC中FasL的表达情况。结果OVX组中破骨细胞的数量较sham组显著升高,凋亡程度降低。OVX+E2组中破骨细胞数量较OVX组数量显著降低,凋亡细胞比例升高。Western blot法结果显示sham组FasL较OVX组显著升高,OVX+E2组FasL较OVX组显著降低。结论雌激素能够降低BMSC中FasL基因的表达,这可能是影响破骨细胞凋亡的因素之一。Objective To explore the effect of decreased Fas ligand （FasL） expression on osteoclast apoptosis in bone marrow-derived mesenchymal stem cells （BMSCs） in the animal model with estrogen deficiency. Methods Animal models of osteoporosis （OP） were established by ovariectomy （OVX, bilateral ovarian resection ） in 8-week-old healthy female mice. BMSCs collected from OVX group, sham operated group or estradiol-stimulated group （OVX ＋ E2） were respectively co-cultured with the osteoclasts from healthy mice. The apoptosis of osteoclasts was compared among the three groups by annexin V-FITC/7-AAD labeling and flow cytometry. FasL expression was detected by Western blotting. Results The apoptosis rate of osteoclasts was significantly higher in both the sham group and the OVX ＋ E2 group than in the OVX group. Western blotting showed that the expression of FasL protein in BMSCs was lower in the OVX group than in the sham group, and it increased in the OVX ＋ E2 group as compared with the OVX group. Conclusion The expression of FasL is down- regulated by estrogen in BMSCs, which may be responsible for the effect of FasL on the apoptosis of osteoclasts.

关 键 词：雌激素 骨质疏松 骨髓间充质干细胞 破骨细胞 FASL 

分 类 号：R392-33[医药卫生—免疫学] R681[医药卫生—基础医学]