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

Ann Rheum Dis. 2015 Nov;74(11):2076-83. doi: 10.1136/annrheumdis-2014-205601. Epub 2014 Jul 10.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects*
  • Diet, High-Fat
  • Dietary Fats / pharmacology
  • Disease Models, Animal
  • Ear Auricle / drug effects*
  • Ear Auricle / injuries
  • Ear Auricle / pathology
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6 / pharmacology*
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Leg Injuries / complications
  • Leg Injuries / pathology*
  • Leptin / metabolism
  • Mice
  • Obesity / complications
  • Osteoarthritis / diagnostic imaging
  • Osteoarthritis / etiology
  • Osteoarthritis / pathology*
  • Osteoarthritis, Knee
  • Resistin / metabolism
  • Stifle / diagnostic imaging
  • Stifle / drug effects*
  • Stifle / injuries
  • Stifle / pathology
  • Synovitis / diagnostic imaging
  • Synovitis / etiology
  • Synovitis / pathology*
  • Tibia / diagnostic imaging
  • Tibia / drug effects
  • Tibial Meniscus Injuries
  • Wound Healing / drug effects*
  • X-Ray Microtomography


  • Dietary Fats
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Leptin
  • Resistin