title: Spontaneous osteoarthritis in Str/ort mice is unlikely due to greater vulnerability to mechanical trauma.
abstract: OBJECTIVE
  Relative contributions of genetic and mechanical factors to osteoarthritis (OA) remain ill-defined. We have used a joint loading model found to produce focal articular cartilage (AC) lesions, to address whether genetic susceptibility to OA in Str/ort mice is related to AC vulnerability to mechanical trauma and whether joint loading influences spontaneous OA development. We also develop finite element (FE) models to examine whether AC thickness may explain any differential vulnerability to load-induced lesions.
  
  
  METHODS
  Right knees of 8-week-old Str/ort mice were loaded, AC integrity scored and thickness compared to CBA mice. Mechanical forces engendered in this model and the impact of AC thickness were simulated in C57Bl/6 mice using quasi-static FE modelling.
  
  
  RESULTS
  Unlike joints in non-OA prone CBA mice, Str/ort knees did not exhibit lateral femur (LF) lesions in response to applied loading; but exhibited thicker AC. FE modeling showed increased contact pressure and shear on the lateral femoral surface in loaded joints, and these diminished in joints containing thicker AC. Histological analysis of natural lesions in the tibia of Str/ort joints revealed that applied loading increased OA severity, proteoglycan loss and collagen type II degradation.
  
  
  CONCLUSIONS
  Genetic OA susceptibility in Str/ort mice is not apparently related to greater AC vulnerability to trauma, but joint loading modifies severity of natural OA lesions in the medial tibia. FE modelling suggests that thicker AC in Str/ort mice diminishes tissue stresses and protects against load-induced AC lesions in the LF but that this is unrelated to their genetic susceptibility to OA.
authors: Lifestyle Research Group, The Royal Veterinary College, Royal College Street, University of London, NW1 0TU, UK. b.poulet@ucl.ac.uk
authors: B
authors: B
authors: Poulet
authors: T A T
authors: TA
authors: Westerhof
authors: R W
authors: RW
authors: Hamilton
authors: S J
authors: SJ
authors: Shefelbine
authors: A A
authors: AA
authors: Pitsillides
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D002358:Cartilage, Articular / Q000293:injuries / Q000473:pathology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013045:Species Specificity; D013314:Stress, Mechanical; D013977:Tibia / Q000473:pathology; D016474:Weight-Bearing / Q000502:physiology