Glucocorticoid-induced differentiation of primary cultured bone marrow mesenchymal cells into adipocytes is antagonized by exogenous Runx2.
Long-term clinical use of glucocorticoids often causes the serious side effect of non-traumatic avascular osteonecrosis. The aim of this study was to examine the effects and mechanisms of a glucocorticoid, dexamethasone (Dex), on differentiation of primary cultured rat bone marrow mesenchymal cells (BMCs). We also tried to block the inhibitory effects of Dex on osteoblast differentiation. Adipocyte markers (peroxisome proliferator-activated receptorgamma-2 and aP2) were increased in response to Dex treatment in a dose- and time-dependent manner, while osteoblastic markers [Runx2, COL 1, osterix, alkaline phosphatase (ALP) and OC] were down-regulated, consistent with ALP and osteocalcin promoter activity. To validate the effects of Runx2 on the expression of osteogenesis and adipocyte genes, pCMV/Flag-Runx2 was transfected into BMCs, and relevant markers were detected after 10(-7) M Dex treatment for 48 h. The results indicated that Dex treatment induced adipogenic differentiation and suppressed proliferation. No significant difference was detected in expressions of these genes between Runx2-transfected cells and Dex-treated BMCs. These data suggest that Dex primarily induced adipocyte differentiation of BMCs. Exogenous Runx2 can antagonize the effect of Dex on osteoblast differentiation.
Lin
Le
L
Departments of Orthopedics, First Affiliated Hospital China Medical University, Shenyang 110001, China.
Dai
Shun-Dong
SD
Fan
Guang-Yu
GY
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley
D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D015675:Osteocalcin; D000469:Alkaline Phosphatase