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

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity and alterations to the gut microbiome contribute to the development of osteoarthritis. Obesity has been shown to enhance joint degeneration in mouse models of post-traumatic osteoarthritis. Most models of osteoarthritis also involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We use a non-surgical animal model of post-traumatic osteoarthritis to determine the effect of obesity on cartilage degeneration two weeks after loading. Cartilage degeneration was caused by a single bout of cyclic compressive tibial loading 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 with normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, mild cartilage degeneration occurred in loaded limbs, as determined by OARSI scores (p<0.001). However, the severity of cartilage damage did not differ among groups (p=0.125). Furthermore, obesity did not enhance cartilage damage in follow-up experiments extended to 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 osteoarthritis phenotypes and complex interactions between biomechanical/metabolic factors in cartilage loss.