MiR-601-induced BMSCs senescence accelerates steroid-induced osteonecrosis of the femoral head progression by targeting SIRT1

BackgroundThe imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is not only the primary pathological feature but also a major contributor to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Cellular senescence is one of the main causes of imbalanced BMSCs differentiation. The purpose of this study was to reveal whether cellular senescence could participate in the progression of SONFH and the related mechanisms.MethodsThe rat SONFH model was constructed, and rat BMSCs were extracted. Aging-related indicators were detected by SA-& beta;-Gal staining, qRT-PCR and Western Blot experiments. Using H2O2 to construct a senescent cell model, and overexpressing and knocking down miR-601 and SIRT1 in hBMSCs, the effect on BMSCs differentiation was explored by qRT-PCR, Western Blot experiment, oil red O staining (ORO), alizarin red staining (ARS), and luciferase reporter gene experiment. A rat SONFH model was established to test the effects of miR-601 and metformin in vivo.ResultsThe current study showed that glucocorticoids (GCs)-induced BMSCs senescence, which caused imbalanced osteogenesis and adipogenesis of BMSCs, was responsible for the SONFH progression. Further, elevated miR-601 caused by GCs was demonstrated to contribute to BMSCs senescence through targeting SIRT1. In addition, the anti-aging drug metformin was shown to be able to alleviate GCs-induced BMSCs senescence and SONFH progression.ConclusionsConsidering the role of BMSCs aging in the progression of SONFH, this provides a new idea for the prevention and treatment of SONFH.

Automated summary

This study revealed that cellular senescence is a major cause of imbalanced differentiation of bone marrow mesenchymal stem cells (BMSCs) and the progression of steroid-induced osteonecrosis of the femoral head (SONFH). MiR-601 and SIRT1 were identified to play important roles in BMSCs senescence, and metformin was shown to alleviate BMSCs senescence and SONFH progression. These findings provide a new perspective for the prevention and treatment of SONFH.