Exosomal miR-150 derived from BMSCs inhibits TNF-α-mediated osteoblast apoptosis in osteonecrosis of the femoral head by GREM1/NF-κB signaling

Regen Med. 2022 Oct;17(10):739-753. doi: 10.2217/rme-2021-0169. Epub 2022 Aug 8.

Abstract

Aim: The purpose of this study was to investigate the functions of exosomal miR-150 derived from bone marrow mesenchymal stem cells in osteonecrosis of the femoral head (ONFH). Materials & methods: Cell viability and apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Alizarin red staining was performed to detect calcium deposits. A rat model was established to assess the effects of exosomal miR-150 on ONFH in vivo. Results: Exosomes or exosomal miR-150 derived from bone marrow mesenchymal stem cells inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy. Exosomal miR-150 suppressed apoptosis and induced autophagy in TNF-α-treated osteoblasts by regulating the GREM1/NF-κB axis. Exosomal miR-150 also improved the pathological features of ONFH in vivo. Conclusion: Exosomal miR-150 alleviates ONFH by mediating the GREM1/NF-κB axis. This study provides a potential therapeutic strategy for ONFH.

Keywords: GREM1/NF-κB; exosomes; miR-150; osteonecrosis of the femoral head.

Plain language summary

Osteonecrosis of the femoral head (ONFH) is an orthopedic disease that frequently occurs in young adults aged less than 50 years. At present, there is no widely accepted curative surgical procedure or drug therapy for this disease. Bone marrow mesenchymal stem cells (BMSCs) play a key role in the progression of ONFH. BMSC-derived exosomes refer to small membrane vesicles that can transfer proteins, miRNAs and mRNAs, which are closely related to the development of ONFH. This study showed that exosomal miRNA-150 derived from BMSCs inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy by regulating the GREM1/NF-κB axis. In addition, exosomal miRNA-150 alleviated the symptoms of ONFH in rats.

MeSH terms

  • Animals
  • Apoptosis
  • Cytokines / metabolism
  • Femur Head
  • MicroRNAs* / genetics
  • NF-kappa B / pharmacology
  • Osteoblasts
  • Osteogenesis
  • Osteonecrosis* / chemically induced
  • Osteonecrosis* / pathology
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Grem1 protein, rat
  • MIRN150 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • Tumor Necrosis Factor-alpha