Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

TitleObesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.
Publication TypeJournal Article
Year of Publication2021
AuthorsLuna M, Guss JD, Vasquez-Bolanos LS, Alepuz AJ, Dornevil S, Strong J, Alabi D, Shi Q, Pannellini T, Otero M, Brito IL, van der Meulen MCH, Goldring SR, Hernandez CJ
JournalJ Orthop Res
Volume39
Issue5
Pagination1007-1016
Date Published2021 05
ISSN1554-527X
KeywordsAnimals, Cartilage, Articular, Gastrointestinal Microbiome, Male, Mice, Mice, Inbred C57BL, Obesity, Osteoarthritis, Tibia, Weight-Bearing
Abstract

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6/J + high-fat diet), mild obesity (toll-like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6/J mice + normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (P < .001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical/metabolic factors in cartilage loss.

DOI10.1002/jor.24799
Alternate JournalJ Orthop Res
PubMed ID32658313
PubMed Central IDPMC7855296
Grant ListR21 AR071534 / AR / NIAMS NIH HHS / United States
R21 AR073454 / AR / NIAMS NIH HHS / United States
DGE-1650441 / / National Science Foundation Graduate Research Fellowships Program /
R21 AR071534 / AR / NIAMS NIH HHS / United States
R21 AR073454 / AR / NIAMS NIH HHS / United States
Related Faculty: 
Tania Pannellini, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700