Arginine Methylation of PPP1CA by CARM1 Regulates Glucose Metabolism and Suppresses Osteoporosis

An imbalance between bone formation by osteoblasts and bone resorption by osteoclasts can lead to osteoporosis. Osteoblasts and osteoclasts have different energy requirements, with aerobic glycolysis being the prominent metabolic feature of osteoblasts, while osteoclast differentiation and fusion are driven by oxidative phosphorylation. Herein, we discovered that coactivator-associated arginine methyltransferase 1 (CARM1) reprogrammed glucose metabolism in osteoblasts and osteoclasts from oxidative phosphorylation to aerobic glycolysis, thereby promoting osteogenic differentiation and inhibiting osteolytic differentiation. Gain-of-function experiments revealed that CARM1 significantly decreased bone loss resulting from ovariectomy in osteoporosis model mice.