From mechanical triggering to metabolic-inflammatory driving: a new paradigm of knee osteoarthritis pathogenesis - PubMed

5 hours ago

Knee osteoarthritis (KOA) is a leading cause of disability, and its understanding has shifted from a passive 'wear-and-tear' process to a more dynamic model.
Abnormal mechanical loading initiates KOA by causing chondrocyte injury and activating pro-inflammatory pathways like NF-κB and Wnt/β-catenin.
Systemic metabolic dysfunction and chronic low-grade inflammation are now seen as key drivers of sustained disease progression, with obesity potentially bridging these factors.
The infrapatellar fat pad may act as a metabolic hub, translating endocrine signals into joint inflammation through adipokines and extracellular vesicles.
Metabolic pathways like CH25H-CYP7B1-RORα are being studied for their role in chondrocyte senescence, with synovial fluid metabolomics explored for biomarkers.
Clinical management should evolve from symptomatic relief to integrated metabolic regulatory strategies, including nutritional interventions and metabolic-modulating pharmacology.
A new paradigm of KOA pathogenesis is defined as 'mechanical initiation, metabolic-inflammatory driving, and heightened mechanical sensitivity' to guide future therapies.

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