Decreased Proliferation and Abnormal Differentiation of Human Mesenchymal Stromal Cells in Steroid-Induced Osteonecrosis of Femoral Head

摘要

>Objectives: To investigate if the pathogenesis of steroid-inducedosteonecrosis of femoral head (ONFH) is associated with abnormalproliferation and differentiation of human mesenchymal stromal cells(MSCs) at the proximal femur.>Methods: Using isolated human MSCs and sections of wholefemoral heads, we analyzed the proliferative capacity and osteogenic,angiogenic and adipogenic differentiation of human MSCs at theproximal femur.>Results: The proliferation of MSCs from patients withcorticosteroid-induced ONFH is decreased. The down-regulatedexpression of BMP2, BMP7, BMP9 and Osteopontin providessupportive evidence corticosteroid-induced inhibition of osteogenesis.Down-regulation of HIF1α, VEGF and VWF by glucocorticoids isdirectly responsible for decreased angiogenesis. Over-expression ofPPARγ2 and (442)aP2 suggests that the corticosteroids may induceMSCs to differentiate into adipocytes.>Conclusions: Our findings suggest steroids may reduce theproliferative activity of MSCs, down-regulate the expression ofosteoblast differentiation factors such as BMP2, BMP7, BMP9 andOPN, decrease angiogenesis by suppressing HIF1α and VEGF, and upregulateadipocyte transcription factor expression such as PPARγ2and (442)aP2.