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Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery\/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery\/fracture. We used a nonsurgical animal model of load\u2010induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6\/J\u2009+\u2009high\u2010fat diet), mild obesity (toll\u2010like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6\/J mice\u2009+\u2009normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery\/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical\/metabolic factors in cartilage loss.<\/jats:p>","DOI":"10.1002\/jor.24799","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T13:55:04Z","timestamp":1594648504000},"page":"1007-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Obesity and load\u2010induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5323-3834","authenticated-orcid":false,"given":"Marysol","family":"Luna","sequence":"first","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Guss","sequence":"additional","affiliation":[{"name":"Meinig School of Biomedical Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S.","family":"Vasquez\u2010Bolanos","sequence":"additional","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Alepuz","sequence":"additional","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Dornevil","sequence":"additional","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Strong","sequence":"additional","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Alabi","sequence":"additional","affiliation":[{"name":"Sibley School of Mechanical and Aerospace Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Meinig School of Biomedical Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Pannellini","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4945-2994","authenticated-orcid":false,"given":"Miguel","family":"Otero","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana L.","family":"Brito","sequence":"additional","affiliation":[{"name":"Meinig School of Biomedical Engineering Cornell University Ithaca New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein C. 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