RGD Reference Report - Histone deacetylase 8 suppresses osteogenic differentiation of bone marrow stromal cells by inhibiting histone H3K9 acetylation and RUNX2 activity. - Rat Genome Database

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Histone deacetylase 8 suppresses osteogenic differentiation of bone marrow stromal cells by inhibiting histone H3K9 acetylation and RUNX2 activity.

Authors: Fu, Yu  Zhang, Ping  Ge, Jie  Cheng, Jie  Dong, Weijie  Yuan, Hua  Du, Yifei  Yang, Mifang  Sun, Ruoxing  Jiang, Hongbing 
Citation: Fu Y, etal., Int J Biochem Cell Biol. 2014 Sep;54:68-77. doi: 10.1016/j.biocel.2014.07.003. Epub 2014 Jul 11.
RGD ID: 13208813
Pubmed: PMID:25019367   (View Abstract at PubMed)
DOI: DOI:10.1016/j.biocel.2014.07.003   (Journal Full-text)

Bone marrow stromal cells (BMSCs) are multipotent progenitor cells with capacities to differentiate into the various cell types and hold great promise in regenerative medicine. The regulatory roles of histone deacetylases (HDACs) in osteoblast differentiation process have been increasingly recognized; however, little is known about the precise roles of HDAC8 in the osteogenic differentiation of BMSCs. Herein we aimed to investigate the roles of HDAC8 in the osteogenic differentiation of rat BMSCs by pharmacological and genetic manipulations in vitro. During osteogenic differentiation of BMSCs, pharmacological inhibition of HDAC8 by HDAC inhibitor valproic acid (VPA) promoted the level of histone H3 lysine 9 acetylation (H3K9Ac) and significantly enhanced the expression of osteogenesis-related genes Runx2, Osterix, osteocalcin (OCN), osteopontin (OPN) and alkaline phosphatase (ALP). Similarly, knockdown of HDAC8 using short interfering RNA triggered H3K9Ac and enhanced osteogenic differentiation of BMSCs, largely phenocopied the effects of VPA-mediated HDAC8 depletion. However, enforced expression of HDAC8 significantly reduced the level of H3K9Ac and inhibited osteogenic differentiation of BMSCs, which can be attenuated by VPA addition. Mechanistically, HDAC8 suppressed osteogenesis-related genes expression by removing the acetylation of histone H3K9, thus leading to transcriptional inhibition during osteogenic differentiation of BMSCs. Importantly, we found that HDAC8 physically associated with Runx2 to repress its transcriptional activity and this association decreased when BMSCs underwent osteogenic differentiation. Taken together, these results indicate that epigenetic regulation of Runx2 by HDAC8-mediated histone H3K9 acetylation is required for the proper osteogenic differentiation of BMSCs.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hdac8Ratnegative regulation of osteoblast differentiation  IMP  RGD 
Hdac8Ratnegative regulation of protein modification process  IMP histone H3-K9 acetylationRGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Runx2Rathistone deacetylase binding  IPIHdac8 (Rattus norvegicus) RGD 
Hdac8Rattranscription factor binding  IPIRunx2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac8  (histone deacetylase 8)
Runx2  (RUNX family transcription factor 2)


Additional Information