Long non-coding RNA XIST promotes osteoporosis by inhibiting the differentiation of bone marrow mesenchymal stem cell by sponging miR-29b-3p that suppresses nicotinamide N-methyltransferase

ABSTRACT

Bone formation is important in the development of osteoporosis (OP). X–inactive specific transcript (XIST), a lncRNA, is involved in this process; however, mode of its action is not known. We compared the serum levels of XIST and miR-29b-3p among the patients with and without OP. In rat bone marrow mesenchymal stem cells (BMSCs), during osteogenic differentiation, XIST expression was detected first, followed by overexpression or suppression of miR-29b-3p and NNMT. Expression of osteogenic genes, ALP (electrochemical alkaline phosphatase) and RUNX2 (Runt-related transcription factor 2) were detected by RT-qPCR and western blots, and the calcium nodules in BMSCs were detected by staining. The relationships of XIST, miR-29b-3p, and NNMT were characterized by dual-luciferase reporter assay. Serum XIST was significantly upregulated in patients of OP. XIST downregulated the ALP and Runx2 levels and inhibited calcium nodules, whereas low expression of XIST reversed these events. MiR-29b-3p was inhibited by XIST sponge and lowered the levels of ALP, Runx2, and calcium nodules. NNMT was negatively regulated by miR-29b-3p, promoting the osteogenic differentiation of BMSCs. In conclusion, XIST is highly expressed in OP, and regulates NNMT by sponging miR-29b-3p to suppress the osteogenic differentiation of BMSCs.

KEYWORDS:

• XIST
• BMSCS
• MIR-29B-3P
• NNMT
• osteoporosis

Highlight

1. XIST is significantly upregulated in osteoporosis.

2. XIST regulates the levels of ALP and Runx2 and interferes with calcium nodules in bone marrow mesenchymal stem cells (BMSCs).

3. XIST/miR-29b-3p/ nicotinamide N-methyltransferase (NNMT) axis suppresses the osteogenic differentiation of BMSCs.

Authors’ contributions

JY performed the experiments and data analysis. MX conceived and designed the study. GR made the acquisition of data. JY and MX did the analysis and interpretation of data. All authors read and approved the manuscript.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Consent to participate

All patients signed written informed consent.

Disclosure statement

No potential conflict of interest was reported by the author (s).

Ethics approval

The present study was approved by the Ethics Committee of the Affiliated Hospital of Jianghan University (Wuhan, China). The processing of clinical tissue samples is in strict compliance with the ethical standards of the Declaration of Helsinki. All patients signed written informed consent.

Supplementary material

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