BMP-2 transgenic alveolar bone-derived marrow stem cells attenuate osteonecrosis of the femoral head

Abstract

Background: Osteonecrosis of the femoral head (ONFH) results in activity-related hip pain and disability, affecting around 20 million people worldwide. However, there is absent of effective therapeutic approaches for ONFH. The transplantation of mesenchymal stem cells was reported to be a promising method for ONFH therapy. In this study, we explored if bone morphogenetic protein-2 (BMP-2) transgenic alveolar bone-derived marrow stem cells (ABMSCs) could be applied to treat ONFH.
 Methods: We established an ONFH mouse model by injection of steroid, and implanted ABMSCs and BMP-2 transgenic ABMSCs into the steroid-impaired femoral head. Gene expression and the pathological alternation of the tissues were analyzed by qRT-PCR and hematoxylin and eosin staining, respectively. Tartrate-resistant acid phosphatase staining was applied to detect osteoclastogenesis. Enzyme linked immunosorbent assay (ELISA) and Western blot were performed to evaluate the protein expression in the sera and tissues, respectively.
 Results: ABMSCs attenuated steroid-induced ONFH and ameliorated the serum concentration of osteogenesis-associated proteins in the ONFH mice. Mechanistically, ABMSCs inhibited osteoclast differentiation by inactivating the RANKL/RANK/OPG signaling pathway. BMP-2 overexpression enhanced ABMSCs to alleviate ONFH.
 Conclusions: ABMSCs and BMP-2 Transgenic ABMSCs attenuate ONFH by promoting osteoblastogenesis and inhibiting osteoclastogenesis via inactivating the RANKL/RANK/OPG signaling pathway.