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An HDAC Inhibitor, Entinostat/MS‐275, Partially Prevents Delayed Cranial Suture Closure in Heterozygous Runx2 Null Mice
Author(s) -
Bae HanSol,
Yoon WonJoon,
Cho YoungDan,
Islam Rabia,
Shin HyeRim,
Kim BongSoo,
Lim JinMuk,
Seo MinSeok,
Cho SeoAe,
Choi KangYoung,
Baek SeungHak,
Kim HongGee,
Woo KyungMi,
Baek JeongHwa,
Lee YunSil,
Ryoo HyunMo
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3076
Subject(s) - runx2 , cleidocranial dysplasia , histone deacetylase , osteoblast , cancer research , biology , epigenetics , microbiology and biotechnology , histone , genetics , in vitro , anatomy , gene , supernumerary
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder caused by mutations in RUNX2 , coding a key transcription factor of early osteogenesis. CCD patients suffer from developmental defects in cranial bones. Despite numerous investigations and clinical approaches, no therapeutic strategy has been suggested to prevent CCD. Here, we show that fetal administration of Entinostat/MS‐275, a class I histone deacetylase (HDAC)‐specific inhibitor, partially prevents delayed closure of cranial sutures in Runx2 +/‐ mice strain of C57BL/6J by two mechanisms: 1) posttranslational acetylation of Runx2 protein, which stabilized the protein and activated its transcriptional activity; and 2) epigenetic regulation of Runx2 and other bone marker genes. Moreover, we show that MS‐275 stimulates osteoblast proliferation effectively both in vivo and in vitro, suggesting that delayed skeletal development in CCD is closely related to the decreased number of progenitor cells as well as the delayed osteogenic differentiation. These findings provide the potential benefits of the therapeutic strategy using MS‐275 to prevent CCD. © 2017 American Society for Bone and Mineral Research.