{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:36:40Z","timestamp":1790206600073,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor \u03baB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin. Although melatonin treatment did not affect the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), it markedly inhibited the activation of NF-\u03baB and subsequent induction of nuclear factor of activated T cell cytoplasmic 1(NFATc1). Thus, our results suggest that melatonin could suppress osteoclast differentiation through downregulation of NF-\u03baB pathway with concomitant decrease in the NFATc1 transcription factor induction. Furthermore, melatonin seems to have an anti-osteoclastogenic effect independent of plasma membrane melatonin receptors. In addition to previously reported properties of melatonin, our study proposes another aspect of melatonin and bone homeostasis.<\/jats:p>","DOI":"10.3390\/ijms18061142","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T04:35:42Z","timestamp":1496118942000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Suppression of Osteoclastogenesis by Melatonin: A Melatonin Receptor-Independent Action"],"prefix":"10.3390","volume":"18","author":[{"given":"Hyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan 626-870, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan 626-870, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Kyoung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan 626-870, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Deok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dental Research Institute and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan 626-870, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/ehjcvp\/pvv037","article-title":"Melatonin has multiorgan effects","volume":"2","author":"Opie","year":"2016","journal-title":"Eur. 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