Adipose Tissue is a Critical Regulator of Osteoarthritis

Abstract

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.

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

“…Leptin levels in synovial fluid may be caused by the diffusion of adipokine from blood into the synovial tissue, but studies with human chondrocytes showed that these cells can express leptin and its long receptor, suggesting a local role of this adipokine [ 27 ] ( Figure 3 ). Despite of this, recent studies using mouse lipodystrophy models show that these mice are protected against OA caused by overweight or cartilage damage, but when these mice recover the adipose tissue, recover the susceptibility to OA [ 91 ]. This evidence shows that adipose tissue is necessary for OA development, but more experiments are necessary to find the role of this tissue in OA progression.…”

Control of mesenchymal cell fate via application of FGF-8b in vitro

“…synovium, adipose, cartilage, ligament, and synovial fluid), that experience physical forces and diverse paracrine signaling events. The main actor in the progression of osteoarthritis is controversial, however a greater appreciation of the role adipose tissue (infrapatellar fat pad) plays in promoting osteoarthritis has recently garnered more interest ( Collins et al, 2021 ; Greif et al, 2020 ). Moreover, the combinatorial application of FGF-2 and FGF-8 in the knee joint was recently found to suppress adipokine secretion and demonstrated a decreased inflammatory profile ( Mengsteab et al, 2020 ).…”

Role of adipose tissues in osteoarthritis

“…Moreover, the femoral heads from OA patients contained high amounts of fat and of n-6 fatty acids, especially arachidonic acid [75] (Figure 3). Early this year, Collins et al proposed that knee joints of lipodystrophic mice were protected from spontaneous or post-traumatic OA, independently from diet [76]. Susceptibility to post-traumatic OA was reintroduced using implantation of AT derived from wild type animals, probably due to the paracrine signalling from fat [76].…”

“…Early this year, Collins et al proposed that knee joints of lipodystrophic mice were protected from spontaneous or post-traumatic OA, independently from diet [76]. Susceptibility to post-traumatic OA was reintroduced using implantation of AT derived from wild type animals, probably due to the paracrine signalling from fat [76]. Nevertheless, lipodystrophic patients have multiple bone abnormalities such as subchondral bone sclerosis, similar to OA patients [77].…”

“…Femoral heads from OA patients contain high amounts of fat, especially arachidonic acid precursor of prostaglandin E2 a known participant on OA inflammation [75]. Lipodystrophic mice were protected from spontaneous or post-traumatic OA, 32 this study proposes that adipose tissue is a critical antagonist of cartilage health and integrity due precisely to the paracrine signalling from fat [76]. Mice without adiponectin-positive progenitors had elevated trabecular bone mass and their vessels within the bone marrow were less in number and high in diameter; characteristics that were far from normal.…”