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

Joo-Hee Choi, Ah‐Ra Jang, Ah-Ra Jang, Min-Jung Park, Dong‐Il Kim, Dong-Il Kim, Jong‐Hwan Park
Endocrinology · 2021 · vol. 162(6) · doi:10.1210/endocr/bqab057 · PMID:33713122 · W3134917369
Lab / animal OA: bronze CC0 ⤵ 1 in-corpus citation
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-11 ⓘ

Melatonin inhibits osteoclastogenesis and bone loss in ovariectomized mice by suppressing RANKL-induced TRAF6, JNK, PRMT1, and NF-κB signaling through a receptor-independent pathway.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

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

My notes (saved in your browser only)

MeSH descriptors

Bone Resorption Melatonin Osteoclasts Animals Bone Diseases, Metabolic Bone Diseases, Metabolic Bone Diseases, Metabolic Bone Diseases, Metabolic Bone Diseases, Metabolic Bone Resorption Bone Resorption Bone Resorption Bone Resorption Cell Differentiation Cell Differentiation Cells, Cultured Down-Regulation Down-Regulation Down-Regulation Female

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cited by (1)

References (70)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:30:20.483728+00:00
License: CC0 · commercial use OK