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Int. J. Mol. Sci. 2017, 18(6), 1142; doi:10.3390/ijms18061142

Suppression of Osteoclastogenesis by Melatonin: A Melatonin Receptor-Independent Action

Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan 626-870, Korea
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
Author to whom correspondence should be addressed.
Academic Editor: Russel J. Reiter
Received: 24 March 2017 / Revised: 15 May 2017 / Accepted: 23 May 2017 / Published: 26 May 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
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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 κB 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-κB 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-κB 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. View Full-Text
Keywords: melatonin; osteoclast; RANKL; NF-κB; NFATc1 melatonin; osteoclast; RANKL; NF-κB; NFATc1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kim, H.J.; Kim, H.J.; Bae, M.-K.; Kim, Y.-D. Suppression of Osteoclastogenesis by Melatonin: A Melatonin Receptor-Independent Action. Int. J. Mol. Sci. 2017, 18, 1142.

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