miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2

Int J Mol Med. 2018 Dec;42(6):3115-3124. doi: 10.3892/ijmm.2018.3891. Epub 2018 Sep 21.

Abstract

MicroRNAs (miRs) are involved in several physiological processes, including chondrogenic differentiation, however, their expression and roles in the chondrogenic differentiation of human adipose‑derived stem cells (hADSCs) remain to be fully elucidated to date. Our previous study showed that miR‑1307‑3p was significantly downregulated during chondrogenic differentiation by microarray and northern blot analysis. The present study aimed to investigate the effects of miR‑1307‑3p on chondrogenic differentiation and the underlying mechanisms. First, the decreased expression of miR‑1307‑3p was confirmed by reverse transcription‑quantitative polymerase chain reaction analysis. Subsequently, gain‑ and loss‑of‑function of miR‑1307‑3p experiments showed that the overexpression of miR‑1307‑3p suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage‑related markers, including sex determining region Y‑box 9, collagen type II α1 chain and aggrecan, whereas the knockdown of miR‑1307‑3p had the opposite effect. In addition, bone morphogenetic protein receptor type 2 (BMPR2) was identified as a target of miR‑1307‑3p. Further mechanistic investigations showed that miR‑1307‑3p attenuated the chondrogenic differentiation of hADSCs at least partly by inhibiting BMPR2‑mothers against decapentaplegic signaling pathways. In conclusion, the findings revealed that miR‑1307‑3p inhibited the chondrogenic differentiation of hADSCs by targeting BMPR2 and its downstream signaling pathway, which may provide novel therapeutic clues for the treatment of cartilage injury.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Bone Morphogenetic Protein Receptors, Type II / metabolism
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Chondrogenesis / genetics*
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • MicroRNAs / genetics*
  • Models, Biological
  • RNA Interference
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism*

Substances

  • MIRN1307 microRNA, human
  • MicroRNAs
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II