M F Rai1, J M Cheverud2, E J Schmidt3, L J Sandell4. 1. Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: rai.m@wustl.edu. 2. Department of Biology, Loyola University, Chicago, IL, United States. Electronic address: jcheverud@luc.edu. 3. School of Physician Assistant Medicine, College of Health Sciences, University of Lynchburg, Lynchburg, VA, United States. Electronic address: schmidt.e@lynchburg.edu. 4. Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: sandelll@wustl.edu.
Abstract
OBJECTIVE: The etiology of osteoarthritis (OA) is unknown, however, there appears to be a significant contribution from genetics. We have identified recombinant inbred strains of mice derived from LG/J (large) and SM/J (small) strains that vary significantly in their ability to repair articular cartilage and susceptibility to post-traumatic OA due to their genetic composition. Here, we report cartilage repair phenotypes in the same strains of mice in which OA susceptibility was analyzed previously, and determine the genetic correlations between phenotypes. DESIGN: We used 12 recombinant inbred strains, including the parental strains, to test three phenotypes: ear-wound healing (n = 263), knee articular cartilage repair (n = 131), and post-traumatic OA (n = 53) induced by the surgical destabilization of the medial meniscus (DMM). Genetic correlations between various traits were calculated as Pearson's correlation coefficients of strain means. RESULTS: We found a significant positive correlation between ear-wound healing and articular cartilage regeneration (r = 0.71; P = 0.005). We observed a strong inverse correlation between articular cartilage regeneration and susceptibility to OA based on maximum (r = -0.54; P = 0.036) and summed Osteoarthritis Research Society International (OARSI) scores (r = -0.56; P = 0.028). Synovitis was not significantly correlated with articular cartilage regeneration but was significantly positively correlated with maximum (r = 0.63; P = 0.014) and summed (r = 0.70; P = 0.005) OARSI scores. Ectopic calcification was significantly positively correlated with articular cartilage regeneration (r = 0.59; P = 0.021). CONCLUSIONS: Using recombinant inbred strains, our study allows, for the first time, the measurement of genetic correlations of regeneration phenotypes with degeneration phenotypes, characteristic of OA (cartilage degeneration, synovitis). We demonstrate that OA is positively correlated with synovitis and inversely correlated with the ability to repair cartilage. These results suggest an addition to the risk paradigm for OA from a focus on degeneration to regeneration.
OBJECTIVE: The etiology of osteoarthritis (OA) is unknown, however, there appears to be a significant contribution from genetics. We have identified recombinant inbred strains of mice derived from LG/J (large) and SM/J (small) strains that vary significantly in their ability to repair articular cartilage and susceptibility to post-traumatic OA due to their genetic composition. Here, we report cartilage repair phenotypes in the same strains of mice in which OA susceptibility was analyzed previously, and determine the genetic correlations between phenotypes. DESIGN: We used 12 recombinant inbred strains, including the parental strains, to test three phenotypes: ear-wound healing (n = 263), knee articular cartilage repair (n = 131), and post-traumatic OA (n = 53) induced by the surgical destabilization of the medial meniscus (DMM). Genetic correlations between various traits were calculated as Pearson's correlation coefficients of strain means. RESULTS: We found a significant positive correlation between ear-wound healing and articular cartilage regeneration (r = 0.71; P = 0.005). We observed a strong inverse correlation between articular cartilage regeneration and susceptibility to OA based on maximum (r = -0.54; P = 0.036) and summed Osteoarthritis Research Society International (OARSI) scores (r = -0.56; P = 0.028). Synovitis was not significantly correlated with articular cartilage regeneration but was significantly positively correlated with maximum (r = 0.63; P = 0.014) and summed (r = 0.70; P = 0.005) OARSI scores. Ectopic calcification was significantly positively correlated with articular cartilage regeneration (r = 0.59; P = 0.021). CONCLUSIONS: Using recombinant inbred strains, our study allows, for the first time, the measurement of genetic correlations of regeneration phenotypes with degeneration phenotypes, characteristic of OA (cartilage degeneration, synovitis). We demonstrate that OA is positively correlated with synovitis and inversely correlated with the ability to repair cartilage. These results suggest an addition to the risk paradigm for OA from a focus on degeneration to regeneration.
Authors: Elizabeth P Blankenhorn; Gregory Bryan; Andrew V Kossenkov; Lise Desquenne Clark; Xiang-Ming Zhang; Celia Chang; Wenhwai Horng; L Susan Pletscher; James M Cheverud; Louise C Showe; Ellen Heber-Katz Journal: Mamm Genome Date: 2009-09-16 Impact factor: 2.957
Authors: Thomas D Brown; Richard C Johnston; Charles L Saltzman; J Lawrence Marsh; Joseph A Buckwalter Journal: J Orthop Trauma Date: 2006 Nov-Dec Impact factor: 2.512
Authors: F W Roemer; A Guermazi; D J Hunter; J Niu; Y Zhang; M Englund; M K Javaid; J A Lynch; A Mohr; J Torner; C E Lewis; M C Nevitt; D T Felson Journal: Osteoarthritis Cartilage Date: 2008-10-17 Impact factor: 6.576
Authors: Muhammad Farooq Rai; Xin Duan; James D Quirk; Nilsson Holguin; Eric J Schmidt; Nobuaki Chinzei; Matthew J Silva; Linda J Sandell Journal: Sci Rep Date: 2017-03-27 Impact factor: 4.379