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