Abstract
Steroid-induced osteonecrosis of femoral head (SONFH) is a common and serious complication caused by long-term and/or excessive use of glucocorticoids (GCs). The decreased activity and abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the major reasons for the onset and progression of this disease. Periostin (POSTN) is a matricellular protein which plays an important role in regulating osteoblast function and bone formation. Sclerostin (SOST) is a secreted antagonist of Wnt signaling that is mainly expressed in osteocytes to inhibit bone formation. However, the exact role of POSTN and SOST in SONFH has not been reported yet. Therefore, we detected the differential expression of POSTN and SOST in BMSCs of SONFH Group patients, and Control Group was patients with traumatic ONFH (TONFH) and developmental dysplasia of the hip (DDH). Furthermore, we used lentiviral transfection to knockdown POSTN expression in BMSCs of patients with SONFH to study the effect of POSTN knockdown on the SOST expression and osteogenic differentiation of BMSCs. The results indicated that the endogenous expression of POSTN and SOST in BMSCs of SONFH Group was upregulated, compared with Control Group. POSTN was upregulated gradually while SOST was downregulated gradually at days 0, 3, and 7 of osteogenic differentiation of BMSCs in Control Group. Contrarily, POSTN was gradually downregulated while SOST was gradually upregulated during osteogenic differentiation of BMSCs in SONFH Group. This could be due to increased expression of SOST in BMSCs, which was caused by excessive GCs. In turn, the increased expression of POSTN in BMSCs may play a role in antagonizing the continuous rising of SOST during the osteogenic differentiation of BMSCs in patients with SONFH. POSTN knockdown significantly attenuated osteo-specific gene expression, alkaline phosphatase activity, and calcium nodule formation in vitro; thus inhibiting the osteogenic differentiation of BMSCs in patients with SONFH. Besides, POSTN knockdown upregulated SOST expression, increased GSK-3β activity, and downregulated β-catenin. These findings suggest that POSTN have an essential role in regulating the expression of SOST and osteogenic differentiation of BMSCs in patients with SONFH, and POSTN knockdown suppresses osteogenic differentiation by upregulating SOST and partially inactivating Wnt/β-catenin signaling pathway. Therefore, targeting POSTN and SOST may serve as a promising therapeutic target for the prevention and treatment of SONFH.
Highlights
Osteonecrosis of the femoral head (ONFH) is reported to be a refractory skeletal disorder bothering over 20 millions of people across the world, and presenting an increasing trend (Chen et al, 2019)
By evaluating the expression levels of SOST and specific osteogenic markers and calcium deposition, we revealed that POSTN knockdown upregulates the expression of SOST and inhibits osteogenic differentiation of human BMSCs (hBMSCs) partly via the Wnt/β-catenin signaling pathway in vitro
These results indicated that the cells cultured in vitro are human MSCs, which meet the criteria of the International Society for Cell Therapy (ISCT) to define MSCs (Dominici et al, 2006)
Summary
Osteonecrosis of the femoral head (ONFH) is reported to be a refractory skeletal disorder bothering over 20 millions of people across the world, and presenting an increasing trend (Chen et al, 2019). The natural history of this disease frequently includes the fracture of the subchondral bone, progressive collapse of the femoral head, and degenerative arthritis with substantial pain and dysfunction of the hip (Mont et al, 2006c). Excessive use of GCs has become one of the most common etiological factors for non-traumatic ONFH because of their anti-inflammatory effects to treat chronic inflammatory diseases such as asthma, arthritis, allergic shock, and inflammatory bowel disease (Mont et al, 2006a; Hartmann et al, 2016). The widespread clinical application of GCs used as adjuvant therapy for epidemic viral pneumonia during outbreaks of coronavirus disease 2019 (COVID-19) (Yang et al, 2020), steroid-induced osteonecrosis of femoral head (SONFH) may further increase in the future. Cell apoptosis and dysfunction of bone marrow mesenchymal stem cells (BMSCs) are considered to be involved in the onset and progression of this disease (Han et al, 2019)
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