The Multifaceted Role of p53 in Musculoskeletal Diseases: A Comprehensive Review.

BACKGROUND

While extensively studied for its central role in tumor suppression (regulating cell cycle, DNA repair, and apoptosis), the p53 gene is now recognized for its significant involvement in musculoskeletal diseases. Aberrant p53 expression and function are key factors in the pathogenesis and progression, although the specific mechanisms and clinical change potential remain incompletely defined.

OBJECTIVE

This review systematically summarizes the multifaceted roles of p53 in major musculoskeletal diseases, analyzes the molecular mechanisms driving disease progression, and evaluates its potential as a therapeutic target.

METHODS

A comprehensive literature search was conducted in PubMed January 2008 to March 2025 using keywords including P53, osteoporosis, osteoarthritis, rheumatoid arthritis, gout, low back pain, and scoliosis. Original research, reviews, and clinical trials focusing on p53 mechanisms were included. 90 relevant articles were selected for analysis.

RESULTS &

CONCLUSION

p53 critically influences the development and progression of musculoskeletal diseases (osteoporosis, osteoarthritis, rheumatoid arthritis, low back pain, gout, and scoliosis) through diverse mechanisms: Disrupting bone formation/resorption balance (via the p53-Nedd4-Runx2 axis in osteoporosis). Promoting chondrocyte apoptosis (via the miR-34a-SIRT1-p53 pathway in osteoarthritis). Modulating inflammatory mediators (TNF-α, IL-6 in rheumatoid arthritis). Regulating oxidative stress responses (p53-SLC2A9 axis in gout). p53 exhibits dual roles (pro-apoptotic vs. anti-inflammatory), necessitating precise targeting strategies. Promising therapeutic interventions include p53-focused gene editing (CRISPR/Cas9), small-molecule inhibitors (PFT-α), and natural products (naringin). However, further clinical validation is essential. Future research requires multidisciplinary approaches to deepen understanding of p53 mechanisms and advance clinical applications in musculoskeletal disorders.