Obesity and Load-induced Post-traumatic Osteoarthritis in the Absence of Fracture or Surgical Trauma.

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of post-traumatic 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 non-surgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration two 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+high fat diet), mild obesity (toll-like receptor 5 deficient, TLR5KO), or normal adiposity (C57Bl6/J mice+normal 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 (p<0.001). 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 six 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 are 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. This article is protected by copyright. All rights reserved.