​Treadmill running modulates infrapatellar fat pad remodeling in osteoarthritic rats in an intensity-dependent manner.

OBJECTIVE: This study aimed to investigate the influence of treadmill running at varying intensities on the remodeling of the infrapatellar fat pad (IFP) in a rat model of osteoarthritis (OA), and to explore the association between exercise-induced IFP alterations and joint pain and structural integrity. METHODS: Thirty male Wistar rats were randomly divided into five groups: control, OA, and three OA groups subjected to treadmill running intensities at low (OAL), medium (OAM), and high (OAH). OA was induced via intra-articular injection of monoiodoacetate. Following induction, rats in the running groups completed a 4-week treadmill running program. Comprehensive evaluations included histomorphological and immunohistochemical analyses, micro-computed tomography, and weight-bearing asymmetry tests to assess pain. Lastly, correlation analyses were performed to assess the relationship between IFP remodeling and joint pain or structural integrity. RESULTS: The OAM group exhibited significant improvements in IFP remodeling, characterized by reduced fibrosis and inflammation (p < 0.05), accompanied by decreased M1 macrophage polarization. Cartilage integrity was better preserved (p < 0.05), and subchondral cortical bone mineral density was significantly higher (p < 0.01) in this group. Likewise, pain severity was significantly alleviated in the OAM group (p < 0.05). In contrast, the OAL and OAH groups displayed no significant improvements. Finally, correlation analysis demonstrated significant associations between IFP fibrosis/inflammation and cartilage damage (r = 0.60), pain (r = 0.58), and trabecular separation (r = 0.38). CONCLUSION: Treadmill running exerts intensity-dependent effects on IFP remodeling in OA rats, with moderate intensity providing optimal benefits. The significant correlations observed between IFP remodeling and joint integrity and pain indicate a potential link between IFP and exercise-induced joint protection.