Survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in osteonecrotic areas are especially important in the treatment of early steroid-induced osteonecrosis of the femoral head (ONFH). We had previously used BMSCs to repair early steroid-induced ONFH, but the transplanted BMSCs underwent a great deal of stress-induced apoptosis and aging in the oxidative-stress (OS) microenvironment of the femoral-head necrotic area, which limited their efficacy. Our subsequent studies have shown that under OS, massive accumulation of damaged mitochondria in cells is an important factor leading to stress-induced apoptosis and senescence of BMSCs. The main reason for this accumulation is that OS leads to upregulation of protein 53 (P53), which inhibits mitochondrial translocation of Parkin and activation of Parkin's E3 ubiquitin ligase, which decreases the level of mitophagy and leads to failure of cells to effectively remove damaged mitochondria. However, P53 downregulation can effectively reverse this process. Therefore, we upregulated Parkin and downregulated P53 in BMSCs. We found that this significantly enhanced mitophagy in BMSCs, decreased the accumulation of damaged mitochondria in cells, effectively resisted stress-induced BMSCs apoptosis and senescence, and improved the effect of BMSCs transplantation on early steroid-induced ONFH.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Achyranthes Bidentata Extract Exerts Osteoprotective Effects on Steroid-Induced Osteonecrosis of the Femoral Head in Rats by Regulating RANKL/RANK/OPG SignalingY Jiang et al. J Transl Med 12, 334. PMID 25471933.ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.
Effect of Bone Mesenchymal Stem Cells Transplantation on the Micro-Environment of Early Osteonecrosis of the Femoral HeadH Song et al. Int J Clin Exp Pathol 8 (11), 14528-34. PMID 26823773.Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head …
The Role of lncRNA RP11-154D6 in Steroid-Induced Osteonecrosis of the Femoral Head Through BMSC RegulationS Xiang et al. J Cell Biochem 120 (10), 18435-18445. PMID 31190361.Our results demonstrated that lncRNA RP11-154D6 might contribute to the progression of steroid-induced ONFH through regulating the behavior of BMSCs and might provide new …
Core Decompression Combined With Autologous Bone Marrow Stem Cells Versus Core Decompression Alone for Patients With Osteonecrosis of the Femoral Head: A Meta-AnalysisZ Wang et al. Int J Surg 69, 23-31. PMID 31301432. - ReviewCompared with core decompression alone in the treatment of ONFH, the combined utilization of core decompression and autologous BMSCs has better pain relief and clinical o …
Deciphering the Molecular Signals of PINK1/Parkin MitophagyTN Nguyen et al. Trends Cell Biol 26 (10), 733-744. PMID 27291334. - ReviewFunctional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenera …
- 81860387/National Natural Science Foundation of China (National Science Foundation of China)
- 81902226/National Natural Science Foundation of China (National Science Foundation of China)
- 5-2/Science and Technology Bureau, Guiyang Municipal Government (Guiyang Municipal Science and Technology Bureau)
- gzwjkj2018-1-008/Department of Health of Guizhou Province (Guizhou Provincial Department of Health)
- gzwjkj2019-1-135/Department of Health of Guizhou Province (Guizhou Provincial Department of Health)