Exosomes from artesunate-treated bone marrow-derived mesenchymal stem cells transferring SNHG7 to promote osteogenesis via TAF15-RUNX2 pathway

Regen Med. 2022 Nov;17(11):819-833. doi: 10.2217/rme-2022-0065. Epub 2022 Oct 2.

Abstract

Aim: Effect of artesunate (ART)-treated bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exos) on osteogenesis and its underlying mechanisms were investigated. Materials & methods: Proliferation, alkaline phosphatase activity and calcified nodule formation of osteoblasts were determined. A mouse model of osteoporosis was established by ovariectomy. Results: SNHG7 was upregulated in BMSC-Exos by twofold, which was further enhanced in ART-BMSC-Exos by about twofold. ART intensified BMSC-Exos-induced proliferation, alkaline phosphatase activity by about fourfold, calcified nodule formation by about threefold and upregulation of osteogenesis related molecules RUNX2 (by 50%), BMP2 (by 30%) and ATF4 (by 40%) via delivering SNHG7. Mechanistically, SNHG7 recruited TAF15 to facilitate RUNX2 stability. Conclusion: ART-BMSC-Exos facilitated osteogenesis via delivering SNHG7 by modulating TAF15/RUNX2 axis.

Keywords: ART; BMSCs; SNHG7; TAF15-RUNX2 axis; exosomes; osteogenesis.

Plain language summary

Osteoporosis is the most common and complex skeletal disorder worldwide. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) have been recognized as an ideal seed source for bone tissue regeneration. We aimed to explore the effect of artesunate (ART)-BMSC-Exos on osteogenesis and its underlying mechanisms. The results showed that ART-BMSC derived exosomal SNHG7 facilitated osteoblast activity and attenuated osteogenesis in mice by modulating TAF15/RUNX2 pathway. Our findings contribute to a better understanding of the therapeutic mechanisms of ART-BMSCs-Exos for osteoporosis and suggest ART-BMSC-Exos as a novel therapeutic option for osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Artesunate / metabolism
  • Artesunate / pharmacology
  • Bone Marrow
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Exosomes*
  • Female
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • Osteogenesis
  • RNA, Untranslated / genetics*
  • TATA-Binding Protein Associated Factors* / metabolism

Substances

  • Core Binding Factor Alpha 1 Subunit
  • MicroRNAs
  • RNA, Untranslated
  • Runx2 protein, mouse
  • TAF15 protein, mouse
  • TATA-Binding Protein Associated Factors
  • Artesunate
  • Alkaline Phosphatase