Clinical and molecular landscape of post-traumatic osteoarthritis.

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown, chronic pain, and disability. Post-traumatic osteoarthritis (PTOA), a secondary form of OA, arises from joint injuries and consistently accounts for a proportion of symptomatic cases. Unlike primary OA, PTOA has a well-defined initiation point, presenting an opportunity for early intervention. Over the past two decades, research has shifted from a cartilage-centric view to a broader understanding of OA as a multifaceted disease involving inflammation, oxidative stress, and complex molecular crosstalk between chondrocytes, synoviocytes, osteocytes, and immune cells. Key inflammatory mediators, such as IL-1β, IL-6, TNF-α, and Wnt/β-catenin signaling, drive disease progression. Advances in imaging, biomarker discovery, and animal models have provided insights into early disease mechanisms. However, gaps remain in understanding the molecular events that trigger PTOA onset, the interplay between joint tissues, and the identification of reliable early biomarkers. Delayed diagnosis, lack of disease-modifying therapies, and OA's complexity remain critical barriers. Future directions should focus on precision medicine integrating biomarkers, imaging, and artificial intelligence for early diagnosis and risk stratification. Emerging regenerative and gene therapies, while promising, would benefit from moving beyond single-pathway targeting, as OA's multifaceted nature makes a combination approach desirable to simultaneously address inflammation, oxidative stress, cartilage matrix degradation, and tissue repair. Multidisciplinary collaborations between clinicians, molecular biologists, and bioengineers are essential to translating discoveries into effective interventions. A paradigm shift toward early, personalized treatment strategies is necessary to improve long-term outcomes in PTOA and OA management.