Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression

Abstract Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that...

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Autores principales:	Younho Han, Young-Mi Kim, Hyung Sik Kim, Kwang Youl Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8abd3e7a392c4121907d750d63812d46
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spelling	oai:doaj.org-article:8abd3e7a392c4121907d750d63812d462021-12-02T12:30:18ZMelatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression10.1038/s41598-017-06304-x2045-2322https://doaj.org/article/8abd3e7a392c4121907d750d63812d462017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06304-xhttps://doaj.org/toc/2045-2322Abstract Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that melatonin enhanced BMP-4-induced osteogenic differentiation and increased the expression of osteogenic markers, especially Osterix, which is an essential transcription factor for the differentiation of preosteoblasts into mature osteoblasts in the late stage of osteoblast differentiation. Melatonin treatment increased the expression of Osterix during osteoblast differentiation and stabilized its expression by the inhibition of ubiquitin-proteasome-mediated degradation of Osterix, leading to up-regulated Osterix transcriptional activity on the osteogenic promoter and promoting alkaline phosphatase activity and bone mineralization. Furthermore, treatment with protein kinase A (PKA) inhibitor H89 and protein kinase C (PKC) inhibitor Go6976 blocked the melatonin-induced transcriptional activity and phosphorylation of Osterix, indicating that melatonin regulates Osterix expression via the PKA and PKC signaling pathways. Overall, these findings suggest that melatonin directly regulates the late stage of osteoblast differentiation by enhancing Osterix expression; this provides further evidence of melatonin as a potent agent for treating osteoporosis.Younho HanYoung-Mi KimHyung Sik KimKwang Youl LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Younho Han Young-Mi Kim Hyung Sik Kim Kwang Youl Lee Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
description	Abstract Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that melatonin enhanced BMP-4-induced osteogenic differentiation and increased the expression of osteogenic markers, especially Osterix, which is an essential transcription factor for the differentiation of preosteoblasts into mature osteoblasts in the late stage of osteoblast differentiation. Melatonin treatment increased the expression of Osterix during osteoblast differentiation and stabilized its expression by the inhibition of ubiquitin-proteasome-mediated degradation of Osterix, leading to up-regulated Osterix transcriptional activity on the osteogenic promoter and promoting alkaline phosphatase activity and bone mineralization. Furthermore, treatment with protein kinase A (PKA) inhibitor H89 and protein kinase C (PKC) inhibitor Go6976 blocked the melatonin-induced transcriptional activity and phosphorylation of Osterix, indicating that melatonin regulates Osterix expression via the PKA and PKC signaling pathways. Overall, these findings suggest that melatonin directly regulates the late stage of osteoblast differentiation by enhancing Osterix expression; this provides further evidence of melatonin as a potent agent for treating osteoporosis.
format	article
author	Younho Han Young-Mi Kim Hyung Sik Kim Kwang Youl Lee
author_facet	Younho Han Young-Mi Kim Hyung Sik Kim Kwang Youl Lee
author_sort	Younho Han
title	Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
title_short	Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
title_full	Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
title_fullStr	Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
title_full_unstemmed	Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
title_sort	melatonin promotes osteoblast differentiation by regulating osterix protein stability and expression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8abd3e7a392c4121907d750d63812d46
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_version_	1718394409188327424

Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression

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