Mechanical strain regulates osteogenesis via Antxr1/LncRNA H19/Wnt/β-catenin axis

J Cell Physiol. 2024 May;239(5):e31214. doi: 10.1002/jcp.31214. Epub 2024 Feb 15.

Abstract

Alleviating bone loss is an essential way to prevent osteoporotic fractures. Proper exercise improves bone density without the side effects of long-term medications, but the mechanism is unclear. Our study explored the role of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of exercise-mediated alleviation of bone loss. Here we discovered that moderate-intensity treadmill exercise alleviates bone loss caused by ovariectomy and ameliorates bone strength accompanied by an increased lncRNA H19 expression. Concomitantly, Antxr1, a mechanosensitive protein was found downregulated by exercise but upregulated by ovariectomy. Interestingly, knockdown expression of Antxr1 increased lncRNA H19 expression and Wnt/β-catenin signaling pathway in bone marrow mesenchymal stem cells, whereas overexpression of Antxr1 decreased lncRNA H19 expression and Wnt/β-catenin signaling pathway. Hence, our study demonstrates the regulation of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of mechanical strain-induced osteogenic differentiation, which provides further mechanistic insight into the role of mechanical regulation in bone metabolism.

Keywords: Antxr1; Wnt/β‐catenin; exercise; lncRNA H19; mechanical strain; osteoporosis.

MeSH terms

  • Animals
  • Bone Density / genetics
  • Cell Differentiation
  • Female
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins* / metabolism
  • Osteogenesis* / genetics
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Ovariectomy / adverse effects
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Receptors, Cell Surface* / metabolism
  • Stress, Mechanical*
  • Wnt Signaling Pathway* / genetics
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • RNA, Long Noncoding
  • Antxr1 protein, mouse
  • Microfilament Proteins
  • Receptors, Cell Surface
  • H19 long non-coding RNA