title: Cartilage and bone changes during development of post-traumatic osteoarthritis in selected LGXSM recombinant inbred mice.
abstract: BACKGROUND
  Little evidence is available on the natural course of osteoarthritis (OA) development and the genes that protect and predispose individuals to it. This study was designed to compare strain-dependent development of OA and its association with tissue regeneration in mice. Two recombinant inbred lines LGXSM-6 and LGXSM-33 generated from LG/J and SM/J intercross were used. Previous studies indicated that LGXSM-6 can regenerate both articular cartilage and ear hole punch while LGXSM-33 cannot.
  
  
  METHODS
  Transection of the medial meniscotibial ligament was performed on 10-week-old male mice to induce OA. Cartilage damage was analyzed by histology and bone morphology was evaluated using micro-computed tomography (CT). Ear punches were performed and evaluated by measurement of residual hole diameter.
  
  
  RESULTS
  Cartilage analysis showed that LGXSM-33 developed a significantly higher grade of OA than LGXSM-6. Bone analysis showed that LGXSM-33 had substantial subchondral bone and trabecular bone thickening 8 weeks post-surgery, while LGXSM-6 showed bone loss over time. We also confirmed that LGXSM-6 can heal ear tissues significantly better than LGXSM-33.
  
  
  CONCLUSIONS
  OA was found to be negatively correlated with the degree of tissue regeneration. LGXSM-33, a poor healer of ear tissues (and articular cartilage), developed more OA compared to LGXSM-6, which had better regenerative ability for ear tissues and articular cartilage. The phenotypic differences observed here are due to genetic differences further suggesting that similar sets of physiological processes and gene variants may mediate variation in OA development and tissue regeneration.
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, MO 63110, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: M F
authors.initials: MF
authors.lastname: Rai
authors.forename: K L
authors.initials: KL
authors.lastname: Janiszak
authors.forename: J M
authors.initials: JM
authors.lastname: Cheverud
authors.forename: L J
authors.initials: LJ
authors.lastname: Sandell
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology* / Q000502:physiology; D004431:Ear, External / Q000293:injuries / Q000502:physiology; D020022:Genetic Predisposition to Disease; D008297:Male; D017888:Medial Collateral Ligament, Knee / Q000293:injuries; D051379:Mice; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012038:Regeneration / Q000502:physiology; D013045:Species Specificity; D014945:Wound Healing / Q000502:physiology; D055114:X-Ray Microtomography