Adipose Tissue is a Critical Regulator of Osteoarthritis

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects obese individuals. The mechanisms by which adipose tissue leads to the onset and progression of OA are unclear due to the complex interactions between the metabolic, biomechanical, and inflammatory factors that accompany obesity. We used a murine model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or post-traumatic OA, on either a chow and high fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to post-traumatic OA was reintroduced into LD mice using implantation of adipose tissue derived from wildtype animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a critical mediator of joint degeneration.