Adipose tissue is a critical regulator of osteoarthritis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-01, Vol.118 (1), p.1-12
• Main Authors: Collins, Kelsey H., Lenz, Kristin L., Pollitt, Eleanor N., Ferguson, Daniel, Hutson, Irina, Springer, Luke E., Oestreich, Arin K., Tang, Ruhang, Choi, Yun-Rak, Meyer, Gretchen A., Teitelbaum, Steven L., Pham, Christine T. N., Harris, Charles A., Guilak, Farshid
• Format: Article
• Language: English
• Subjects: Adipogenesis; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Adipose Tissue - transplantation; Adiposity; Animals; Arthritis; Biomechanics; Biomedical materials; Body Weight; Cartilage - pathology; Cytokines - metabolism; Degeneration; Diet, High-Fat - adverse effects; Disease Models, Animal; Disease Susceptibility - complications; Disease Susceptibility - metabolism; Embryo fibroblasts; Female; Fibroblasts; Fibroblasts - metabolism; High fat diet; Hyperplasia - complications; Inflammation; Inflammation - metabolism; Joint diseases; Lipodystrophy; Lipodystrophy - diagnostic imaging; Lipodystrophy - genetics; Lipodystrophy - metabolism; Lipodystrophy - physiopathology; Locomotion; Male; Mice; Muscle Strength; Obesity; Osteoarthritis; Osteoarthritis, Knee - complications; Osteoarthritis, Knee - diagnostic imaging; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - prevention & control; Pain - complications; Paracrine Communication - physiology; Paracrine signalling; Physical Sciences
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2021096118

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.