RRC ID 51850
Author Chen W, Chen L, Zhang Z, Meng F, Huang G, Sheng P, Zhang Z, Liao W.
Title MicroRNA-455-3p modulates cartilage development and degeneration through modification of histone H3 acetylation.
Journal Biochim. Biophys. Acta
Abstract Histone acetylation regulated by class I histone deacetylases (HDACs) plays a pivotal role in matrix-specific gene transcription and cartilage development. While we previously demonstrated that microRNA (miR)-455-3p is upregulated during chondrogenesis and can enhance early chondrogenesis, the mechanism underlying this process remains largely unclear. In this study, we characterized the effect of miR-455-3p on histone H3 acetylation and its role during cartilage development and degeneration. We observed that miR-455-3p was highly expressed in proliferating and pre-hypertrophic chondrocytes, while HDAC2 and HDAC8 were primarily expressed in hypertrophic chondrocytes. Meanwhile, miR-455-3p suppressed the activity of reporter constructs containing the 3'-untranslated regions of HDAC2/8, inhibited HDAC2/8 expression and promoted histone H3 acetylation at the collagen 2 (COL2A1) promoter in human SW1353 chondrocyte-like cells. Treatment with the HDAC inhibitor trichostatin A (TSA) resulted in increased expression of cartilage-specific genes and promoted glycosaminoglycan deposition. Moreover, TSA inhibited matrix metalloproteinase 13 (Mmp13) expression and promoted nuclear translocation of SOX9 in interleukin-1-treated primary mouse chondrocytes. Lastly, knockdown of HDAC2/3/8 increased SRY (sex-determining region Y)-box 9 (SOX9) and decreased Runt-related transcription factor 2 (RUNX2) expression. Taken together, these findings suggest that miR-455-3p plays a critical role during chondrogenesis by directly targeting HDAC2/8 and promoting histone H3 acetylation, which raises possibilities of using miR-455-3p to influence chondrogenesis and cartilage degeneration.
Volume 1863(12)
Pages 2881-2891
Published 2016-12
DOI 10.1016/j.bbamcr.2016.09.010
PII S0167-4889(16)30230-0
PMID 27638301
MeSH 3' Untranslated Regions Acetylation / drug effects Animals Base Sequence Binding Sites Cartilage / cytology Cartilage / metabolism Cell Line, Tumor Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / drug effects Chondrogenesis / genetics* Collagen Type II / genetics Collagen Type II / metabolism Core Binding Factor Alpha 1 Subunit / genetics Core Binding Factor Alpha 1 Subunit / metabolism Histone Deacetylase 2 / antagonists & inhibitors Histone Deacetylase 2 / genetics Histone Deacetylase 2 / metabolism Histone Deacetylase Inhibitors / pharmacology Histone Deacetylases / genetics Histone Deacetylases / metabolism Histones / genetics Histones / metabolism* Humans Hydroxamic Acids / pharmacology Interleukin-1 / pharmacology Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism Mice MicroRNAs / genetics* MicroRNAs / metabolism Primary Cell Culture Protein Processing, Post-Translational* Repressor Proteins / antagonists & inhibitors Repressor Proteins / genetics Repressor Proteins / metabolism SOX9 Transcription Factor / antagonists & inhibitors SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism Signal Transduction
IF 3.438
Human and Animal Cells ATDC5(RCB0565)