TY - JOUR
T1 - Heritability of articular cartilage regeneration and its association with ear wound healing in mice
AU - Rai, Muhammad Farooq
AU - Hashimoto, Shingo
AU - Johnson, Eric E.
AU - Janiszak, Kara L.
AU - Fitzgerald, Jamie
AU - Heber-Katz, Ellen
AU - Cheverud, James M.
AU - Sandell, Linda J.
PY - 2012/7
Y1 - 2012/7
N2 - 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. Conclusion. 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.
AB - 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. Conclusion. 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.
UR - http://www.scopus.com/inward/record.url?scp=84860503265&partnerID=8YFLogxK
U2 - 10.1002/art.34396
DO - 10.1002/art.34396
M3 - Article
C2 - 22275233
AN - SCOPUS:84860503265
SN - 0004-3591
VL - 64
SP - 2300
EP - 2310
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 7
ER -