title: 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 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.
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA Department of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Deeptee
authors.initials: D
authors.lastname: Jain
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jenna N
authors.initials: JN
authors.lastname: McNeill
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Little
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA Rothman Institute Cartilage Center, Rothman Institute, Philadelphia, Pennsylvania, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Anderson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Huebner
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA Department of Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA Department of Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, USA Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA Department of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina, USA Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D054644:Ear Auricle / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D007869:Leg Injuries / Q000150:complications / Q000473:pathology*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000150:complications; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D020370:Osteoarthritis, Knee; D052243:Resistin / Q000378:metabolism; D013264:Stifle / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D013585:Synovitis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D000070600:Tibial Meniscus Injuries; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D020738:Leptin; D052243:Resistin