Fibrosis of the infrapatellar fat pad induces gradual cartilage degeneration in a rat model.

Abstract

Knee osteoarthritis (OA), a degenerative joint disease, causes pain and reduced activity levels, with prevalence increasing with age. Knee OA is recognized as a "joint organ disease," where interactions between the articular cartilage, meniscus, synovium, and infrapatellar fat pad (IFP) are critical. Obesity contributes to OA not only through mechanical stress but also via systemic and local inflammation mediated by adipose tissue. Adiponectin, an adipokine with anti-inflammatory and chondroprotective effects, shows levels negatively correlated with obesity and positively correlated with OA severity. This study explored the role of IFP in OA progression using a rat model of monoiodoacetic acid-induced IFP fibrosis. In vivo, IFP and cartilage degeneration were assessed via histological analysis, real-time PCR, and RNA sequencing. Ex vivo, the effects of conditioned media from synovial cells and IFP on chondrocytes were evaluated. Findings revealed that fibrosis reduced adiponectin expression and accelerated OA progression. Gene sequencing showed significant metabolic pathway changes, particularly in fatty acid β-oxidation, indicating impaired IFP function. Conditioned media from inflamed IFP negatively affected chondrocytes by reducing anabolic factors and increasing cartilage-degrading enzymes. These results suggest that IFP degeneration contributes to OA by promoting inflammation and cartilage degradation. Targeting IFP fibrosis and fatty acid metabolism may offer therapeutic potential to mitigate OA progression.