Steroid induced adipogenesis: may be the pathogenesis of osteonecrosis of the femoral head

Abstract

Objective To explore the role of the steroids induced adipogenesis in pathogenesis ot glucocorticoid-induced osteonecrosis of the femoral head (ONFH).Methods Femoral heads respectively diagnosed glucocortcoid-induced ONFH and osteoarthritis (OA),which were obtained during total hip arthroplasty,were made histopathological and immunohistochemistry study.Osteoblasts cultured in DMEM (H) medium with 10％ FBS supplemented with dexamethasone in different concentrations (0,1×10-8,1×10-7,1×10-6 mol/L) were divided into 3 groups.Three groups were received alizarin red staining and oil red O staining at different time.The expression of PPAR-γand Runx2 were performed by immunohistochemistry study.SD rats were injected high-dose of methylprednisolone to establish a steroid-induced ONFH model.At 12th weeks after intervention,histopathological and immunohistochemistry were performed for the presence of osteonecrosis and adipogeneisis,Runx2 and PPAR-γ expression in the femoral head.Results The number and the size of adipocytes significantly increased in ONFH group by comparison with OA group.The expression of PPAR-γ was increased while Runx2 expression was decreased in ONFH group,compared to the OA group.Compared with control group,dexamethasone (1 ×10-6,10-7 mol/L) significantly induced the mRNA expression of PPAR-γ,while the expression of Runx2 was significantly decreased.Osteoblasts treated with 10-6 mol/L dexamethasone can promote osteoblast transdifferentiated into adipocytes.Evidence of osteonecrosis and adipogenesis were observed in steroid treated rats.The number and the size of adipocytes were increased significantly compared with control group.At the same time,the expression of PPAR-γ was increased and the Runx2 was decreased.Conclusion The steroids stimulating the PPAR-γ expression and inhibiting the Runx2 expression,which resulted in BMSCs differentiating into adipocytes and inhibited osteoblasts differentiation activity,may be one of important pathogenesis mechanism of steroid-induced ONFH. Key words: Femur head necrosis; Glucocorticoids; Osteocytes; Adipocytes