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.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- XIST:
-
X-inactive-specific transcript
- FBXW7:
-
F-box and WD repeat domain-containing 7
- IRF-1:
-
interferon regulatory factor-1
- BMSC:
-
bone marrow mesenchymal stem cell
- OVX:
-
ovariectomy
- OM:
-
osteogenic medium
- BMP2:
-
bone morphogenetic protein-2
- OCN:
-
osteocalcin
- OPN:
-
osteopontin
- RUNX2:
-
RUNX Family Transcription Factor 2
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This work was sponsored by Fujian provincial health technology project (No.2021CXA013)
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Conception of manuscript: EIP working group (all authors).
Manuscript design and writing: Chenyang Song, Yu Guo, Fenyong Chen.
Manuscript reviewing and editing: all authors.
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Song, C., Guo, Y., Chen, F. et al. IRF-1-inhibited lncRNA XIST regulated the osteogenic differentiation via miR-450b/FBXW7 axis. Apoptosis 28, 669–680 (2023). https://doi.org/10.1007/s10495-023-01820-w
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DOI: https://doi.org/10.1007/s10495-023-01820-w