Bone mesenchymal stem cells (BMSCs) are the most commonly investigated progenitor cells in bone tissue engineering for treating severe bone defects. Strategies for regulating BMSC differentiation fate have received wide attention, in which redox homeostasis plays an important role due to the change in energy metabolism during stem cell differentiation. In the present study, it was observed that autophagic activity was induced along with BMSC osteogenic differentiation and subsequently regulated reactive oxygen species (ROS) generation and the level of osteogenesis. Furthermore, it was also observed that neuropeptide substance P (SP) administration could enhance the autophagic activity in rat BMSCs via the AMPK and mTOR pathways, as well as decreasing ROS generation and promoting osteogenic differentiation. Inhibition of autophagic activity by 3-MA reversed the effects of SP on ROS and osteogenic levels. The present results indicated that autophagic activity participated in the regulation of differentiation fate of BMSCs and SP could promote osteogenic differentiation by activating autophagy, providing a more precise biological mechanism for its application in bone tissue engineering.
The purpose of this study was to evaluate the efficacy of core decompression with a biomaterial-loaded allograft threaded cage (ATC) for the treatment of femoral head osteonecrosis in an established goat model. First, bilateral early-stage osteonecrosis was induced. After core decompression, the remaining goats were randomly divided into three groups: Group A, the goats were left without any treatment; Group B, the goats were treated with implanting a composite of autologous bone and decalcified bone matrix (DBM); Group C, the goats were treated using insertion of ATC loaded with DBM and autogenous bone graft. Then radiographic, histological and biomechanical analysis were taken in each group at 5, 10, and 20 weeks postoperation. In Group A, the classical signs of osteonecrosis of the femoral head were identified 10 weeks after the induction. Twenty weeks later, the density, surface and biomechanical stability of the femoral head were normal in Group C, while an irregular surface and an inhomogeneous microstructure or variation of density/hardness were identified in Group B. The specimens revealed a continuous trabaecular bone structure throughout the cage and extensive bone ingrowth and remodeling in Group C, while fibrous tissue was evident in Group B. Core decompression with a biomaterial loaded ATC almost uniformly delays or arrests the progression of the disease before articular collapse, and it could help to get the balance between bone resorption and new bone formation, strengthen structural mechanics of the femoral head, provide structure support of articular cartilage.
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