FNDC5 inhibits autophagy of bone marrow mesenchymal stem cells and promotes their survival after transplantation by downregulating Sp1

Wei, Huan; Liu, Shuaiye; Wang, Tingting; Li, Yanping; Liu, Kangmei; Guo, Qunying; Li, Ling

doi:10.1038/s41420-023-01634-4

Cited by 3 publications

(1 citation statement)

References 57 publications

(75 reference statements)

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“…However, the detailed mechanism of miR-150-5p on the osteogenic differentiation of BMSCs has not been further studied by Geng Y, et al, but miR-150-5p has been found to inhibit the osteogenic differentiation of ankylosing spondylitis fibroblasts [ 14 ] and adipose-derived stem cells [ 15 ]. At the same time, it is well known that the protein encoded by the FNDC5 gene (iris) has been found to regulate the differentiation of BMSCs [ 16 , 17 ], including promoting the osteogenic differentiation of BMSCs [ 18 ]. Therefore, miR-150-5p may be involved in the regulation of osteogenic differentiation of BMSCs by regulating the expression of FNDC5.…”

Section: Introductionmentioning

confidence: 99%

mir-150-5p inhibits the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting irisin to regulate the p38/MAPK signaling pathway

Qi,

Zhang,

Dong

et al. 2024

J Orthop Surg Res

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Purpose To study the effect of miR-150-5p on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and further explore the relationship between its regulatory mechanism and irisin. Methods We isolated mouse BMSCs, and induced osteogenic differentiation by osteogenic induction medium. Using qPCR to detect the expression of osteogenic differentiation-related genes, western blot to detect the expression of osteogenic differentiation-related proteins, and luciferase reporter system to verify that FNDC5 is the target of miR-150-5p. Irisin intraperitoneal injection to treat osteoporosis in mice constructed by subcutaneous injection of dexamethasone. Results Up-regulation of miR-150-5p inhibited the proliferation of BMSCs, and decreased the content of osteocalcin, ALP activity, calcium deposition, the expression of osteogenic differentiation genes (Runx2, OSX, OCN, OPN, ALP and BMP2) and protein (BMP2, OCN, and Runx2). And down-regulation of miR-150-5p plays the opposite role of up-regulation of miR-150-5p on osteogenic differentiation of BMSCs. Results of luciferase reporter gene assay showed that FNDC5 gene was the target gene of miR-150-5p, and miR-150-5p inhibited the expression of FNDC5 in mouse BMSCs. The expression of osteogenic differentiation genes and protein, the content of osteocalcin, ALP activity and calcium deposition in BMSCs co-overexpressed by miR-150-5p and FNDC5 was significantly higher than that of miR-150-5p overexpressed alone. In addition, the overexpression of FNDC5 reversed the blocked of p38/MAPK pathway by the overexpression of miR-150-5p in BMSCs. Irisin, a protein encoded by FNDC5 gene, improved symptoms in osteoporosis mice through intraperitoneal injection, while the inhibitor of p38/MAPK pathway weakened this function of irisin. Conclusion miR-150-5p inhibits the osteogenic differentiation of BMSCs by targeting irisin to regulate the/p38/MAPK signaling pathway, and miR-150-5p/irisin/p38 pathway is a potential target for treating osteoporosis.

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