Evidence for Genetic Contribution to Variation in Posttraumatic Osteoarthritis in Mice

Arthritis & Rheumatology
Nobuaki ChinzeiLinda J Sandell

Abstract

Recombinant inbred mouse strains generated from an LG/J and SM/J intercross offer a unique resource to study complex genetic traits such as osteoarthritis (OA). We undertook this study to determine the susceptibility of 14 strains to various phenotypes characteristic of posttraumatic OA. We hypothesized that phenotypic variability is associated with genetic variability. Ten-week-old male mice underwent surgical destabilization of the medial meniscus (DMM) to induce posttraumatic OA. Mice were killed 8 weeks after surgery, and knee joints were processed for histology to score cartilage degeneration and synovitis. Micro-computed tomography was used to analyze trabecular bone parameters including subchondral bone plate thickness and synovial ectopic calcifications. Gene expression in the knees was assessed using a QuantiGene Plex assay. Broad-sense heritability ranged from 0.18 to 0.58, which suggested that the responses to surgery were moderately heritable. The LGXSM-33, LGXSM-5, LGXSM-46, and SM/J strains were highly susceptible to OA, while the LGXSM-131b, LGXSM-163, LGXSM-35, LGXSM-128a, LGXSM-6, and LG/J strains were relatively OA resistant. This study was the first to accomplish measurement of genetic correlations of phenoty...Continue Reading

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Citations

Jun 14, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Xiaoyan LiTaitao Sun
May 3, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhenhan DengJohnny Huard
Oct 24, 2019·Tissue Engineering. Part a·Susan D'CostaBrian O Diekman
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Jul 6, 2020·BMC Musculoskeletal Disorders·Anand O Masson, Roman J Krawetz
Jan 12, 2021·Molecular Therapy. Nucleic Acids·Long ZhangYankun Li
Apr 10, 2021·Arthritis Research & Therapy·Mukundan AtturMuhammad Farooq Rai
Nov 18, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mingming YanMuhammad Farooq Rai

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