MiR-145 inhibits the differentiation and proliferation of bone marrow stromal mesenchymal stem cells by GABARAPL1 in steroid-induced femoral head necrosis.

Abstract

Steroid-induced osteonecrosis of femoral head (SANFH) involves impaired differentiation of bone marrow mesenchymal stem cells (BMSC), the mechanism of which is regulated by multiple microRNAs. Studies have shown that miR-145 is a key regulatory molecule of BMSC cells, but its mechanism in steroid-induced femur head necrosis remains unclear. The present study mainly explored the specific mechanism of miR-145 involved in SANFH. In this study dexamethasone, a typical glucocorticoid, was used to induce osteogenic differentiation of BMSC cells. Western blot, qPCR, CCK8 and flow cytometry were used to investigate the effects of miR-145 on the proliferation and differentiation of BMSC. The relationship between miR-145 and GABA Type A Receptor Associated Protein Like 1(GABARAPL1) was identified using dual luciferase reports and the effects of the two molecules on BMSC were investigated in vitro. The results showed that miR-145 was up-regulated in SANFH patients, while GABARAPL1 was down-regulated. Inhibition of miR-145 can improve apoptosis and promote proliferation and activation of BMSC. GABARAPL1 is a downstream target gene of miR-145 and is negatively regulated by miR-145. In conclusion, miR-145 regulates the proliferation and differentiation of glucocorticoid-induced BMSC cells through GABARAPL1 and pharmacologically inhibit targeting miR-145 may provide new aspect for the treatment of SANFH.

• Authors: Pengfei Xu, Jun Chang, Guangwen Ma, Faxue Liao, Tangbing Xu, Yunfeng Wu, Zongsheng Yin
• Journal: BMC musculoskeletal disorders (BMC Musculoskelet Disord) Vol. 23 Issue 1 Pg. 1020 (Nov 26 2022) ISSN: 1471-2474 [Electronic] England
• PMID: 36435763 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Glucocorticoids
• MicroRNAs
• Steroids
• GABARAPL1 protein, human
• Microtubule-Associated Proteins
• Adaptor Proteins, Signal Transducing
• MIRN145 microRNA, human

Topics

• Humans
• Osteogenesis
• Femur Head Necrosis (chemically induced, metabolism)
• Femur Head (metabolism)
• Glucocorticoids (adverse effects)
• Bone Marrow
• Mesenchymal Stem Cells (metabolism)
• MicroRNAs (metabolism)
• Steroids
• Cell Proliferation
• Microtubule-Associated Proteins (metabolism, pharmacology)
• Adaptor Proteins, Signal Transducing (genetics)