MicroRNA-455-3p modulates cartilage development and degeneration through modification of histone H3 acetylation

作者：Chen, Weishen; Chen, Lingwu; Zhang, Ziji; Meng, Fangang; Huang, Guangxin; Sheng, Puyi; Zhang, Zhiqi^*; Liao, Weiming^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2016, 1863(12): 2881-2891.

DOI：10.1016/j.bbamcr.2016.09.010

• miR-455-3p
• Class I HDACs
• Histone acetylation
• Cartilage-specific genes
• Chondrogenesis

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-l-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.

• 出版日期2016-12
• 单位中山大学