基础医学与临床2017,Vol.37Issue(6):786-791,6.
下调骨细胞TGF-β/Smad4信号可抑制小鼠BMSCs成骨及破骨分化
Down-regulation of osteocytic TGF-β/Smad4inhibits the osteoblastic and osteoclastic differentiation in mouse BMSCs
摘要
Abstract
Objective To determine the effect of ostecytic TGF-β/Smad4 signaling on osteoblastic and osteoclastic differentiation in bone marrow stromal cells (BMSCs).Methods Mice with osteocytic TGF-β/Smad4 conditional knock down (Smad4ot CKD) were generated as previously by crossing DMP1-8kb-Cre mice with Smad4lox(ex8)/lox(ex8) mice.The osteocytes were isolated from tibial and femoral diaphysis and co-cultured with wild-type BMSCs.ALP staining, Alizarin red staining and TRAP staining were performed to show osteoblastic and osteoclastic differentiation.Then, their marker genes were detected by qPCR and proteins measured by Western blot.ResultsThe expression of Runx2 and Osterix were reduced in smad4 CKDot co-cultured with BMSCs compared with controls(P<0.01).Similarly, the specific markers of osteoblastic differentiation were decreased (P<0.01).Additionally, the expression of RANKL was not significantly changed in with BMSCs.However, OPG was highly expressed incontrol group compared with smad4 CKD in co-cultured group (P<0.05).Thus, the radio of RANKL/OPG was significantly reduced (P<0.05).Furthermore, the expression of RANK was inhibited.Conclusions The terminally-differentiated osteocytes are the cells regulating bone metabolism, while down-regulation of osteocytic-TGF-β/Smad4 inhibits BMSC osteoblastic and osteoclastic differentiation.关键词
骨细胞/TGF-β/Smad4/BMSCs/成骨分化/破骨分化Key words
osteocyte/TGF-β/Smad4/BMSCs/osteoblastic differentiation/osteoclastic differentiation分类
医药卫生引用本文复制引用
代光明,任磊,陈虹,刘文,陈宇,何小强,刘伟,涂小林,黄伟..下调骨细胞TGF-β/Smad4信号可抑制小鼠BMSCs成骨及破骨分化[J].基础医学与临床,2017,37(6):786-791,6.基金项目
国家自然科学基金(81371972, 81572142) (81371972, 81572142)