Effects of dietary fatty acid content on humeral cartilage and bone structure in a mouse model of diet‐induced obesity

Abstract

Obesity is a primary risk factor for osteoarthritis (OA), and previous studies have shown that dietary content may play an important role in the pathogenesis of cartilage and bone in knee OA. Several previous studies have shown that the ratio of ω‐3 polyunsaturated fatty acids (PUFAs), ω‐6 PUFAs, and saturated fatty acids can significantly influence bone structure and OA progression. However, the influence of obesity or dietary fatty acid content on shoulder OA is not well understood. The goal of this study was to investigate the role of dietary fatty acid content on bone and cartilage structure in the mouse shoulder in a model of diet‐induced obesity. For 24 weeks, mice were fed control or high‐fat diets supplemented with ω‐3 PUFAs, ω‐6 PUFAs, or saturated fatty acids. The humeral heads were analyzed for bone morphometry and mineral density by microCT. Cartilage structure and joint synovitis were determined by histological grading, and microscale mechanical properties of the cartilage extracellular and pericellular matrices were quantified using atomic force microscopy. Diet‐induced obesity significantly altered bone morphology and mineral density in a manner that was dependent on dietary free fatty acid content. In general, high‐fat diet groups showed decreased bone quality, with the ω‐3 diet being partially protective. Cartilage mechanical properties and OA scores showed no changes with obesity or diet. These findings are consistent with clinical literature showing little if any relationship between obesity and shoulder OA (unlike knee OA), but suggest that diet‐induced obesity may influence other joint tissues. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

The burden of metabolic syndrome on osteoarthritic joints

“…Those with greater levels of ω-6 PUFAs had significantly worse outcomes, as well as increased leptin and decreased adiponectin levels [64]. However, this is controversial with others demonstrating mice fed with a ω-6-rich diet over a 24-week period to have no increased risk of synovitis when compared to those fed with ω-3 PUFAs [65]. Despite these differing results, PUFA derivatives have been trialled therapeutically.…”

Skeletal dysplasia-causing TRPV4 mutations suppress the hypertrophic differentiation of human iPSC-derived chondrocytes

“…The 10 µm cryosection with cryofilm was fixed on a microscope slide using chitosan and stored at 4 ºC overnight. The next day, cryosections were mechanically loaded using an atomic force microscopy (AFM, MFP-3D Bio, Asylum Research, Goleta, CA) as previously described (Votava, Schwartz, Harasymowicz, Wu, & Guilak, 2019). Briefly, the samples were tested in PBS at 37 ºC to maintain hydration and mimic physiologic conditions, respectively.…”

Obesity alters the collagen organization and mechanical properties of murine cartilage

“…As an alternative to in vivo testing, diet-induced obese mouse models have been used to study OA pathogenesis 17 – 20 primarily due to their accelerated OA onset and progression. Using a mouse model provides the opportunity to directly evaluate changes in both histological and mechanical cartilage properties in the context of diet-induced obesity.…”

“…Recent studies have demonstrated increased cartilage strains in participants with high BMI 15,16 . Because it is difficult to directly evaluate cartilage mechanical properties in vivo, it is unclear whether these increased strains are due to elevated joint loading, decreased cartilage stiffness, or a combination of both.As an alternative to in vivo testing, diet-induced obese mouse models have been used to study OA pathogenesis [17][18][19][20] primarily due to their accelerated OA onset and progression. Using a mouse model provides…”

“…As an alternative to in vivo testing, diet-induced obese mouse models have been used to study OA pathogenesis [17][18][19][20] primarily due to their accelerated OA onset and progression. Using a mouse model provides…”