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Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression

Title
Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression
Author
김영미
Keywords
MESENCHYMAL STEM-CELLS; BONE-FORMATION; SIGNALING PATHWAYS; OVARIECTOMIZED RATS; OSTEOGENIC ACTIVITY; PHOSPHORYLATION; ACTIVATION; INCREASES; P38; OSTEOPOROSIS
Issue Date
2017-07
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v. 7, Article no. 5716
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.
URI
https://www.nature.com/articles/s41598-017-06304-xhttp://repository.hanyang.ac.kr/handle/20.500.11754/72217
ISSN
2045-2322
DOI
10.1038/s41598-017-06304-x
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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