RT Journal Article
SR Electronic
T1 Adipose Tissue is a Critical Regulator of Osteoarthritis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.04.134601
DO 10.1101/2020.06.04.134601
A1 Kelsey H. Collins
A1 Kristin L. Lenz
A1 Eleanor N. Pollitt
A1 Daniel Ferguson
A1 Irina Hutson
A1 Luke E. Springer
A1 Arin K. Oestreich
A1 Ruhang Tang
A1 Yun-Rak Choi
A1 Gretchen A. Meyer
A1 Steven L. Teitelbaum
A1 Christine T.N. Pham
A1 Charles A. Harris
A1 Farshid Guilak
YR 2020
UL http://biorxiv.org/content/early/2020/06/12/2020.06.04.134601.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.