miR-892b Inhibits Hypertrophy by Targeting KLF10 in the Chondrogenesis of Mesenchymal Stem Cells

Abstract

We investigated the functional role of miR-892b as a novel inhibitor of chondrocyte hypertrophy during TGF-β-mediated chondrogenesis of human mesenchymal stem cells (hMSCs). The expression of miR-892b during TGF-β-mediated chondrogenesis of hMSCs and the effects of miR-892b overexpression on chondrogenic and hypertrophic marker genes in the chondrogenesis of hMSCs were investigated. Targets of miR-892b were identified and verified by overexpression of synthetic miRNA mimics and luciferase assays. Cross-talk between Kruppel-like factor 10 (KLF10) and Indian hedgehog (Ihh) was investigated using KLF10 knockdown (KD). miR-892b enhanced chondrogenic makers and suppressed hypertrophy in hMSC chondrogenesis, mimicking parathyroid hormone-related peptide (PTHrP). KLF10, a transcription factor and miR-892b target, directly regulated Ihh promoter activity. Like miR-892b, KLF10 KD enhanced hMSC chondrogenesis and inhibited hypertrophy. Our findings suggest a key role of miR-892b in targeting the KLF10-Ihh axis as a regulator of hypertrophy in TGF-β-mediated chondrogenesis of hMSCs and provide a novel strategy for preventing hypertrophy in chondrogenesis from MSCs. Keywords: chondrogenesis, mesenchymal stem cells, hypertrophy, miR-892b, KLF10