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Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Ha-Neui | - |
dc.contributor.author | Lee, Jong-Ho | - |
dc.contributor.author | Bae, Suk-Chul | - |
dc.contributor.author | Ryoo, Hyun-Mo | - |
dc.contributor.author | Ha, Hyunil | - |
dc.contributor.author | Lee, Zang Hee | - |
dc.contributor.author | Kim, Hong-Hee | - |
dc.date.accessioned | 2013-01-21T06:50:58Z | - |
dc.date.available | 2013-01-21T06:50:58Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Journal of Bone and Mineral Research; Vol.26, No.9, pp.2161-2173 | ko_KR |
dc.identifier.issn | 0884-0431 | - |
dc.identifier.uri | https://hdl.handle.net/10371/80874 | - |
dc.description.abstract | Histone deacetylases (HDACs) deacetylate both histones and nonhistone proteins and play a key role in the regulation of physiologic and aberrant gene expression. Inhibition of HDACs has emerged as a promising therapeutic target for cancer and neurologic diseases. In this study we investigated the osteogenic effect and mechanism of action of MS-275, a class I HDAC inhibitor with preference for HDAC1. Both local and systemic administration of MS-275 stimulated bone regeneration in animal models. MS-275 stimulated mRNA expression and activity of the early osteogenic marker tissue-nonspecific alkaline phosphatase (TNAP) in bone tissue and osteogenic cells. By using a series of TNAP promoter deletion constructs and a DNA affinity precipitation assay, we identified DExH-box helicase Dhx36 as a factor that binds to the MS-275 response element in the TNAP promoter. We also found that Dhx36 binding to the MS-275 response element is crucial for MS-275 induction of TNAP transcription. Dhx36 physically interacted with a subset of HDACs (HDAC1 and -4) whose protein levels were downregulated by MS-275, and forced expression of these HDACs blunted the stimulatory effects of MS-275 by a deacetylase activity-independent mechanism(s). Taken together, the results of our study show that MS-275 induces TNAP transcription by decreasing the interaction of HDAC1/4 with Dhx36, which can at least in part contribute to the bone anabolic effects of MS-275. ⓒ 2011 American Society for Bone and Mineral Research. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | American Society for Bone and Mineral Research | ko_KR |
dc.subject | DHX36 | ko_KR |
dc.subject | TISSUE-NONSPECIFIC ALKALINE PHOSPHATASE (TNAP) | ko_KR |
dc.subject | HISTONE DEACETYLASE | ko_KR |
dc.subject | MS-275 | ko_KR |
dc.subject | OSTEOBLAST | ko_KR |
dc.title | Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 김하늬 | - |
dc.contributor.AlternativeAuthor | 이종호 | - |
dc.contributor.AlternativeAuthor | 배석철 | - |
dc.contributor.AlternativeAuthor | 류현모 | - |
dc.contributor.AlternativeAuthor | 하현일 | - |
dc.contributor.AlternativeAuthor | 이장희 | - |
dc.contributor.AlternativeAuthor | 김홍희 | - |
dc.identifier.doi | 10.1002/jbmr.426 | - |
dc.citation.journaltitle | Journal of Bone and Mineral Research | - |
dc.description.tc | 3 | - |
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