Glucocorticoid‐induced differentiation of primary cultured bone marrow mesenchymal cells into adipocytes is antagonized by exogenous Runx2

Lin L, Dai S‐Dong, Fan G‐Yu. Glucocorticoid‐induced differentiation of primary cultured bone marrow mesenchymal cells into adipocytes is antagonized by exogenous Runx2. APMIS 2010; 118: 595–605. 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 receptorγ‐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.