The role of p53 in musculoskeletal diseases

Du Yanli; Wang Yi; Wang Zhenyu; Wang Xuanhui; Li Xinye; Xiong Xifeng; Miao Haixiong

doi:10.12307/2026.612

Abstract：BACKGROUND:The p53 gene is a key tumor suppressor gene that was initially extensively studied for its central roles in cell cycle regulation,DNA repair,and apoptosis.In recent years,studies have shown that p53 also plays important roles in the pathogenesis of musculoskeletal diseases.Abnormal expression and dysfunction of p53 are considered important factors in the development and progression of these diseases.However,the specific mechanisms and clinical translation potential of p53 have not yet been systematically elucidated. OBJECTIVE:To comprehensively summarize the multiple roles of p53 in musculoskeletal diseases,analyze the molecular mechanisms by which p53 influences disease progression,and evaluate its potential as a therapeutic target across these diseases. METHODS:PubMed was searched for literature published from January 2004 to December 2024 using the keywords of"P53,osteoporosis,post-menopausal osteoporosis,osteoarthritis,degenerative arthritis,rheumatoid arthritis,gout,low back pains,low back ache,back pain,scoliosis"in English.We included original studies,reviews,and clinical trials while excluding non-English articles and studies unrelated to the mechanisms of interest.A total of 81 articles were ultimately selected for comprehensive analysis. RESULTS AND CONCLUSION:p53 is involved in the occurrence and development of musculoskeletal diseases through mechanisms such as regulating the balance of bone formation and resorption(e.g.,the p53-Nedd4-Runx2 axis),chondrocyte apoptosis(e.g.,the miR-34a-SIRT1-p53 pathway),inflammatory mediators(e.g.,tumor necrosis factor-α/interleukin-6),and oxidative stress(e.g.,the p53-SLC2A9 axis).Its dual roles(pro-apoptotic and anti-inflammatory)suggest the need for precise regulation of p53 activity.Intervention strategies based on gene editing(e.g.,CRISPR/Cas9),small-molecule inhibitors(e.g.,PFT-α),and natural products(e.g.,naringin)show therapeutic potential,but further clinical validation is needed.In the future,it is necessary to combine multidisciplinary approaches to deepen p53 mechanism research and clinical practice.