Abstract
Novel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.
Highlights
Steroid-induced osteonecrosis of the femoral head (SONFH), a joint dysfunction caused by long-term heavy use of glucocorticoids, results in a high rate of disability
We investigated the role of PARK7 in promoting resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells (BMSCs)
Our results show that PARK7 promoted disintegration of the Kelch-like echinacoside–associated protein 1 (Keap1)–nuclear factor (erythroid-derived 2)–like 2 (Nrf2) complex, which led to activation of Nrf2
Summary
Steroid-induced osteonecrosis of the femoral head (SONFH), a joint dysfunction caused by long-term heavy use of glucocorticoids, results in a high rate of disability. Effective early-stage treatment strategies are urgently needed in the field of orthopedics [1, 2]. Cells with bone regeneration ability such as bone marrow mesenchymal stem cells (BMSCs) have been used to treat early-stage SONFH. The survival of the cells seeded into the osteonecrotic area is key to achieving successful transplantation [3, 4]. We used BMSCs to construct tissue-engineered bone for the repair of earlystage SONFH. Transplantation efficacy was not satisfactory mainly because numerous BMSCs transplanted into the osteonecrotic area underwent stress-induced apoptosis [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
