Glucocorticoid Enhanced the Expression of Ski in Osteonecrosis of Femoral Head: The Effect on Adipogenesis of Rabbit BMSCs

Glucocorticoid (GC)-induced osteonecrosis has been considered as the most serious side effect in long-term or over-dose steroid therapy. The decreased bone mass and increased marrow fat tissue demonstrated that GC can destroy the normal differentiation of bone marrow mesenchymal stem cells (BMSCs), which accelerates adipogenesis but not osteogenesis. However, the underlying mechanisms are still unclear. Ski, an evolutionary conserved protein, is a multifunctional transcriptional regulator that involved in regulating signaling pathways associated with adipogenesis differentiation, but the concrete function remains unclear. In this work, we first established a methylprednisolone (MPS)-induced osteonecrosis of femoral head (ONFH) rabbit model, in which the expression of Ski, PPAR-γ, and FABP4 was up-regulated compared with control group, and then we induced the isolated BMSCs from rabbit with dexamethasone (Dex) in vitro and the results showed that the Ski expression was up-regulated by Dex in a dose- and time-dependent manner. Therefore, we demonstrated that the expression of Ski was up-regulated in glucocorticoid-related osteonecrosis disease in vivo and in vitro. Moreover, the adipogenesis differentiation capacity of BMSCs was enhanced after induced by Dex, which was identified by Oil Red O staining, and the up-regulated PPAR-γ and FABP4 expression. To further study the function of Ski in BMSC after induced by Dex, Ski specific small interfering RNA (Ski-siRNA) was used. Results showed that knockdown of Ski obviously decreased adipogenesis differentiation evident by Oil Red O staining, and the expression of PPAR-γ and FABP4 was down-regulated simultaneously. Collectively, our findings suggest that Ski increased significantly during glucocorticoid-induced adipogenic differentiation of BMSCs, and the expression level was consistent with adipogenic-related proteins including PPAR-γ and FABP4. Based on the above data, we believe that Ski might become a new molecule in the treatment of GC-induced ONFH and our study could provide a basis for further study on the detailed function of Ski in ONFH.