IRF-1-inhibited lncRNA XIST regulated the osteogenic differentiation via miR-450b/FBXW7 axis

Apoptosis. 2023 Apr;28(3-4):669-680. doi: 10.1007/s10495-023-01820-w. Epub 2023 Feb 17.

Abstract

Osteoporosis influences life quality among elder people. Osteoblast dysfunction could cause the occurrence of osteoporosis. LncRNA XIST are involved in the progression of osteoporosis. However, the correlation between IRF-1 and XIST in osteogenic differentiation remains unclear. In the study, Clinical samples were collected for the analysis of XIST level. mRNA and protein levels were detected by RT-qPCR and western blot, respectively. H&E staining was performed to observe the histological changes in mice. Alizarin Red Staining was applied to assess the calcium deposits in hBMSCs. Meanwhile, the relation among XIST, miR-450b and FBXW7 was investigated by dual luciferase assay and ChIP. In vivo model was constructed to assess the impact of XIST in osteoporosis. XIST was found to be upregulated in osteoporosis, and XIST overexpression could inhibit the osteogenic differentiation in hBMSCs. IRF-1 could transcriptionally inhibit the expression of XIST, and XIST could inhibit osteogenic differentiation through binding with miR-450b in hBMSCs. In addition, miR-450b significantly promoted the osteogenic differentiation in hBMSCs via targeting FBXW7. Furthermore, XIST knockdown could inhibit the symptom of osteoporosis in vivo. IRF-1 promoted the osteogenic differentiation via mediation of lncRNA XIST/miR-450b/FBXW7 axis, and this finding might shed novel insights on exploring new ideas against osteoporosis.

Keywords: FBXW7; IRF-1; Osteogenic differentiation; XIST; miR-450b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation / genetics
  • Cells, Cultured
  • F-Box-WD Repeat-Containing Protein 7 / genetics
  • F-Box-WD Repeat-Containing Protein 7 / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteogenesis / genetics
  • Osteoporosis* / genetics
  • Osteoporosis* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • MicroRNAs
  • RNA, Long Noncoding
  • Irf1 protein, mouse