Adipose tissue is a critical regulator of osteoarthritis

Abstract

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or 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 posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.

Experimental evidence that physical activity inhibits osteoarthritis: Implications for inferring activity patterns from osteoarthritis in archeological human skeletons

“…Excess body weight likely affects OA degeneration by producing a combination of adiposity‐induced metaflammation and abnormal joint loading (Berenbaum et al, 2018; Zapata‐Linares et al, 2021). In this study, body weight does not explain differences in knee OA degeneration between physically active and sedentary animals since body weights were similar between the two groups, but it remains possible that sedentary animals had greater relative adiposity, and hence adiposity‐induced metaflammation (Collins et al, 2021). Second, routine physical activity while young may help promote growth of stronger joint tissues that are more resistant to OA degeneration later in life (Helminen et al, 2000).…”

β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis

“…This fits to the most recent findings demonstrating that adipose tissue plays a critical role in the pathophysiology of OA. The authors described that leptin-mediated effects, rather than body weight, play a predominant role in joint degeneration ( 62 ). Interestingly, leptin levels were only elevated in Adrb2 -/- DMM but not in Adrb2 -/- Sham mice, although body weight and fat mass were not different.…”

Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease

“…Adipose tissue may be considered an organ [ 30 ] owing to its ability in secreting cytokines, interleukins, growth factors and adipokines. Such growth factors are present in synovial fluid [ 31 ] and can determine the metabolism of cartilage and synovium [ 32 ]. In particular, leptin and adiponectin are adipokines secreted in large quantities only by adipose tissue, but found also in the synovial fluid.…”