Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury

Abstract

Objective The mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of dietary fatty acids, adipokines, and body weight following joint injury in mouse model of OA. Methods Mice were fed high-fat diets rich in various fatty acids (FAs) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilizing the medial meniscus. Wound healing was evaluated using an ear punch. OA, synovitis and wound healing were determined histologically, while bone changes were measured using microCT. Activity levels and serum cytokines were measured at various time-points. Multivariate models were performed to elucidate the associations of dietary, metabolic, and mechanical factors with OA and wound healing. Results Using weight-matched mice and multivariate models, we found that OA was significantly associated with dietary fatty acid content and serum adipokine levels, but not with body weight. Furthermore, spontaneous activity of the mice was independent of OA development. Small amounts of ω-3 PUFAs (8% by kcal) in a high-fat diet were sufficient to mitigate injury-induced OA, decreasing leptin and resistin levels. ω-3 PUFAs significantly enhanced wound repair, SFAs or ω-6 PUFAs independently increased OA severity, heterotopic ossification, and scar tissue formation. Conclusions Our results indicate that dietary FA content is a primary regulator of OA severity and wound regeneration with obesity, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA.

Effects of Dietary Saturated Fatty Acids on the Onset and Progression of Osteoarthritis in Rat Knee Joints

“…This is consistent with the reported increase in palmitate-or stearic acid-induced apoptosis in chondrocytes [225,240]. In addition, previous studies have reported that SFA-rich high-fat diet increased the severity of OA [12,121,160].…”

“…The ω-3 PUFA diet decreased the progression of OA and synovitis, while the ω-6 PUFA and the SFA diet increased the progression of the disease [121]. Thus the study concluded that dietary composition and not body weight was associated with worsening of the disease.…”

“…Also, free fatty acids may be involved in inflammatory metabolic diseases such as obesity and inflammatory joint diseases [173]. Thus, dietary saturated fatty acids (SFA) could initiate the link between OA and obesity [121,223,224]. This is supported by the alterations in subchondral bone structure in patients with increased SFA intake [145] that may lead to OA.…”

“…A Recent study showed the effects of n-3 fatty acids to alleviate inflammation in the joints [152]. Furthermore, dietary FA has also been shown to regulate wound healing and severity of OA [121]. Taken together, the current literature suggests the role of FA and OA has been extensively studied.…”

“…It has also been recently found that 'palmitic acid exerts proapoptotic and pro-inflammatory' actions in the articular cartilage, acting in conjunction with IL-1β to facilitate chondrocyte death and cartilage destruction [153]. Wu C.L et al compared a low-fat diet and an SFA diet for wound healing properties and concluded that SFA significantly worsened OA [121]. This result was in cohesion with previous studies showing the effect of SFA-rich high fat diet increases the severity of OA [12,160].…”