Melatonin Inhibits Osteoclastogenesis and Bone Loss in Ovariectomized Mice by Regulating PRMT1-Mediated Signaling

Abstract Melatonin, a pineal gland hormone, has been suggested to treat postmenopausal osteoporosis due its inhibitory effect on osteoclast differentiation. We previously reported that protein arginine methyltransferase 1 (PRMT1) was an important mediator of receptor activator nuclear factor-?B ligand (RANKL)-induced osteoclastogenesis. However, the relationship between melatonin and PRMT1 in differentiation estrogen deficiency–induced is unclear. In this study, we investigated mechanisms vitro vivo by focusing PRMT1. Melatonin treatment effectively blocked RANKL-induced osteoclastogenesis inhibiting asymmetric dimethylarginine (ADMA) expression. tumor necrosis factor receptor-associated 6 (TRAF6) phosphorylation JNK were also suppressed melatonin, TRAF6 siRNA attenuated p-JNK production. inhibited transcriptional activity NF-?B interfering with binding subunit p65 RANKL-treated bone marrow–derived macrophages. Our results revealed inhibits expression through receptors-independent pathway. Thus, anti-osteoclastogenic mediated cascade inhibition TRAF6, JNK, PRMT1, signaling vivo, ovariectomy caused significant decreases mineral density, but alleviated ovariectomized (OVX)-induced loss resorption. Furthermore, TRAP mRNA upregulated OVX-femurs, injection. These findings suggest suppressing cascades