title: Heritability of articular cartilage regeneration and its association with ear wound healing in mice.
abstract: OBJECTIVE
  Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology, but little information is available on the genetics of cartilage regeneration. Therefore, this study was undertaken to investigate cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred (RI) lines generated from LG/J (healer of ear wounds) and SM/J (nonhealer) inbred mouse strains.
  
  
  METHODS
  An acute full-thickness cartilage injury was introduced in the trochlear groove of 8-week-old mice (n=265) through microsurgery. Mouse knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For the ear wound phenotype, a bilateral 2-mm through-and-through puncture was created in 6-week-old mice (n=229), and healing outcomes were measured after 30 days. Broad-sense heritability and genetic correlations were calculated for both phenotypes.
  
  
  RESULTS
  Time-course analysis of the RI mouse lines showed no significant regeneration until 16 weeks after surgery; at that time, the strains could be segregated into 3 categories: good, intermediate, and poor healers. Analysis of heritability (H2) showed that both cartilage regeneration (H2=26%; P=0.006) and ear wound closure (H2=53%; P<0.00001) were significantly heritable. The genetic correlations between the two healing phenotypes for common inbred mouse strains (r=0.92) and RI mouse lines (r=0.86) were found to be extremely high.
  
  
  CONCLUSIONS
  Our findings indicate that articular cartilage regeneration in mice is heritable, the differences between the mouse lines are due to genetic differences, and a strong genetic correlation between the two phenotypes exists, indicating that they plausibly share a common genetic basis. We therefore surmise that LG/J by SM/J intercross mice can be used to dissect the genetic basis of variation in cartilage regeneration.
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
authors.forename: Muhammad Farooq
authors.initials: MF
authors.lastname: Rai
authors.forename: Shingo
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Eric E
authors.initials: EE
authors.lastname: Johnson
authors.forename: Kara L
authors.initials: KL
authors.lastname: Janiszak
authors.forename: Jamie
authors.initials: J
authors.lastname: Fitzgerald
authors.forename: Ellen
authors.initials: E
authors.lastname: Heber-Katz
authors.forename: James M
authors.initials: JM
authors.lastname: Cheverud
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Sandell
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology*; D004423:Ear / Q000293:injuries / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*