Treatment with senolytic drugs ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting osteoclastogenesis.

Peng Wang, Meiyue Yang, Weijian Liu, Chao Chen

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Osteonecrosis of the femoral head (ONFH) is a disabling orthopedic disease characterized by hyperactivation of osteoclasts and impairment of osteogenesis. However, the underlying mechanism by which osteoclastogenesis is driven in ONFH remains unclear. Although cellular senescence is hypothesized to contribute to the development of multiple comorbidities, the role of cellular senescence in ONFH remains underexplored. In this study, we explored whether clearing senescent cells ameliorates ONFH. Analyses of single-cell sequencing data revealed that the population of osteoclasts increased in ONFH, and the expression of senescence-related genes (CDKN1A and CDKN2A) in macrophages was elevated in ONFH patients. Additionally, we found that senescent macrophages in ONFH mice were significantly increased, as evidenced by an increased population of SA-β-gal positive cells and F4/80

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Research summary

The paper claims that treatment with senolytic drugs can ameliorate steroid-induced osteonecrosis of the femoral head by inhibiting osteoclastogenesis. This research is relevant as it explores the role of cellular senescence in a specific age-related condition, potentially addressing underlying mechanisms of aging-related diseases.

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