Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury
- Chia-Lung Wu1,2,
- Deeptee Jain1,
- Jenna N McNeill1,
- Dianne Little1,
- John A Anderson1,3,
- Janet L Huebner4,
- Virginia B Kraus4,
- Ramona M Rodriguiz5,6,7,
- William C Wetsel4,5,6,7,8,
- Farshid Guilak1,2,8
- 1Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA
- 2Department of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina, USA
- 3Rothman Institute Cartilage Center, Rothman Institute, Philadelphia, Pennsylvania, USA
- 4Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
- 5Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA
- 6Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA
- 7Department of Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, USA
- 8Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA
- Correspondence to Dr Farshid Guilak, Department of Orthopaedic Surgery, Duke University Medical Center, 375 Medical Sciences Research Bldg., Box 3093, Durham, NC 27710, USA;
- Received 21 March 2014
- Revised 29 May 2014
- Accepted 1 June 2014
- Published Online First 10 July 2014
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 fatty acids, adipokines, and body weight on OA following joint injury in an obese mouse model.
Methods Mice were fed high-fat diets rich in various fatty acids (FA) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilising 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 with obesity, dietary FA content regulates wound healing and OA severity following joint injury, independent of body weight, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA.