Print Email Facebook Twitter High-fat feeding primes the mouse knee joint to develop osteoarthritis and pathologic infrapatellar fat pad changes after surgically induced injury Title High-fat feeding primes the mouse knee joint to develop osteoarthritis and pathologic infrapatellar fat pad changes after surgically induced injury Author Warmink, K. Kozijn, A.E. Bobeldijk, I. Stoop, R. Weinans, H. Korthagen, N.M. Publication year 2020 Abstract Objective. Obesity is one of the greatest risk factors for osteoarthritis (OA) and evidence is accumulating that inflammatory mediators and innate immunity play an important role. The infrapatellar fat pad (IPFP) could be a potential local source of inflammatory mediators in the knee. Here, we combine surgical joint damage with high-fat feeding in mice to investigate inflammatory responses in the IPFP during OA development. Design. Mice (n = 30) received either a low-fat diet (LFD), high-fat diet (HFD) for 18 weeks or switched diets (LFD > HFD) after 10 weeks. OA was induced by surgical destabilization of the medial meniscus (DMM), contralateral knees served as sham controls. An additional HFD-only group (n = 15) received no DMM. Results. The most pronounced inflammation, characterized by macrophage crown-like structures (CLS), was found in HFD + DMM mice, CLS increased compared to HFD only (mean difference = 7.26, 95%CI [1.52–13.0]) and LFD + DMM (mean difference = 6.35, 95%CI [0.53–12.18). The M1 macrophage marker iNOS increased by DMM (ratio = 2.48, 95%CI [1.37–4.50]), while no change in M2 macrophage marker CD206 was observed. Fibrosis was minimal by HFD alone, but in combination with DMM it increased with 23.45% (95%CI [13.67–33.24]). Conclusions. These findings indicate that a high-fat diet alone does not trigger inflammation or fibrosis in the infrapatellar fat pad, but in combination with an extra damage trigger, like DMM, induces inflammation and fibrosis in the infrapatellar fat pad. These data suggest that HFD provides a priming effect on the infrapatellar fat pad and that combined actions bring the joint in a metabolic state of progressive OA. Subject OsteoarthritisInflammationMacrophagesMetabolic obesityFibrosisAnimal model To reference this document use: http://resolver.tudelft.nl/uuid:ee78e6d0-9818-44ca-bd0f-8a28a2f66e78 DOI https://doi.org/10.1016/j.joca.2020.03.008 TNO identifier 875718 Source Osteoarthritis and Cartilage, 28 (28), 593-602 Bibliographical note pdf including supplementary data Document type article Files To receive the publication files, please send an e-mail request to TNO Library.