Arginine promotes angio-osteogenesis by attenuating oxidative stress-induced bone loss and ameliorating mitophagy

Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. Development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. Arginine is a semi-essential amino acid that is involved in numerous biological processes. Several studies have demonstrated its effects on NO production, protein biosynthesis, and immune responses. In this study, the specific effect of arginine on osteoporosis was explored. We found that arginine attenuates bone loss in aged mice. Indeed, arginine was found to promote osteogenesis and angiogenesis in these animals. Moreover, we showed that arginine can increase the activity of vascular endothelial cells and promote osteogenesis, whereas it inhibited adipogenesis in vitro. In addition, we found an effect of arginine on mitochondria in osteoblast-lineage and endothelial cells. Specifically, arginine altered the expression of PINK1/Parkin or Bnip3 in mitochondria of these cells, thereby promoting mitophagy, and protecting cells from ROS. Similarly, arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model. In conclusion, arginine supplementation might be an effective therapy in the treatment of osteoporosis.