title: Effect of muscle weakness and joint inflammation on the onset and progression of osteoarthritis in the rabbit knee.
abstract: OBJECTIVE
  Interactions between mechanical and non-mechanical independent risk factors for the onset and progression of Osteoarthritis (OA) are poorly understood. Therefore, the goal of the present study was to investigate the in vivo effects of muscle weakness, joint inflammation and the combination on the onset and progression of OA in a rabbit knee joint model.
  
  
  METHODS
  Thirty 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were divided into four groups with one limb randomly assigned to be the experimental side: (1) surgical denervation of the vastus lateralis (VL) muscle; (2) muscle weakness induced by intramuscular injection of Botulinum toxin A (BTX-A); (3) intraarticular injection with Carrageenan to induce a transient inflammatory reaction; (4) combination of Carrageenan and BTX-A injection. After 90 days, cartilage histology of the articular surfaces were microscopically analyzed using the Osteoarthritis Research Society International (OARSI) histology scoring system.
  
  
  RESULTS
  VL denervation resulted in significantly higher OARSI scores in the patellofemoral joint (group 1). BTX-A administration resulted in significant cartilage damage in all four compartments of the knee (group 2). Carrageenan did not cause significant cartilage damage. BTX-A combined with Carrageenan lead to severe cartilage damage in all four compartments.
  
  
  CONCLUSIONS
  Muscle weakness lead to significant OA in the rabbit knee. A transient local inflammatory stimulus did not promote cartilage degradation nor did it enhance OA progression when combined with muscle weakness. These results are surprising and add to the literature the conclusion that acute inflammation is probably not an independent risk factor for OA in this rabbit model.
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Orthopaedic Department, University Hospital, University of Basel, Basel, Switzerland. Electronic address: christian.egloff@usb.ch.
authors.forename: C
authors.initials: C
authors.lastname: Egloff
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. Electronic address: asawatsky@ucalgary.ca.
authors.forename: A
authors.initials: A
authors.lastname: Sawatsky
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. Electronic address: tleonard@ucalgary.ca.
authors.forename: T
authors.initials: T
authors.lastname: Leonard
authors.affiliation: McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Alberta, Canada. Electronic address: hartd@ucalgary.ca.
authors.forename: D A
authors.initials: DA
authors.lastname: Hart
authors.affiliation: Orthopaedic Department, University Hospital, University of Basel, Basel, Switzerland. Electronic address: Victor.valderrabano@usb.ch.
authors.forename: V
authors.initials: V
authors.lastname: Valderrabano
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. Electronic address: wherzog@ucalgary.ca.
authors.forename: W
authors.initials: W
authors.lastname: Herzog
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018908:Muscle Weakness / Q000150:complications* / Q000175:diagnosis; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000209:etiology*; D011817:Rabbits
keywords: BTX-A; Carrageenan; Joint inflammation; Muscle weakness; Osteoarthritis; Rabbit model