Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis

J Orthop Surg Res. 2023 Jan 30;18(1):73. doi: 10.1186/s13018-023-03538-6.

Abstract

Objective: Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform.

Materials and methods: In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).

Results: miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303.

Conclusions: Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.

Keywords: Cochlin; Competing endogenous RNA; KCNMA1-AS1; Osteogenic differentiation; Osteoporosis; miR-1303.

MeSH terms

  • Cell Differentiation / genetics
  • Cells, Cultured
  • Extracellular Matrix Proteins* / genetics
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • MicroRNAs* / genetics
  • Osteogenesis / genetics
  • Osteoporosis* / genetics
  • RNA, Antisense / genetics

Substances

  • KCNMA1 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • MicroRNAs
  • MIRN1303 microRNA, human
  • COCH protein, human
  • Extracellular Matrix Proteins
  • RNA, Antisense