title: Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis.
abstract: Joint injury causes post-traumatic osteoarthritis (PTOA). About ∼50% of patients rupturing their anterior cruciate ligament (ACL) will develop PTOA within 1-2 decades of the injury, yet the mechanisms responsible for the development of PTOA after joint injury are not well understood. In this study, we examined whole joint gene expression by RNA sequencing (RNAseq) at 1 day, 1-, 6-, and 12 weeks post injury, in a non-invasive tibial compression (TC) overload mouse model of PTOA that mimics ACL rupture in humans. We identified 1446 genes differentially regulated between injured and contralateral joints. This includes known regulators of osteoarthritis such as MMP3, FN1, and COMP, and several new genes including Suco, Sorcs2, and Medag. We also identified 18 long noncoding RNAs that are differentially expressed in the injured joints. By comparing our data to gene expression data generated using the surgical destabilization of the medial meniscus (DMM) PTOA model, we identified several common genes and shared mechanisms. Our study highlights several differences between these two models and suggests that the TC model may be a more rapidly progressing model of PTOA. This study provides the first account of gene expression changes associated with PTOA development and progression in a TC model. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:474-485, 2017.
authors.affiliation: Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, 7000 East Ave, L-452, Livermore, California, 94550.|UC Merced, School of Natural Sciences, Merced, California.
authors.forename: Jiun C
authors.initials: JC
authors.lastname: Chang
authors.affiliation: Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, 7000 East Ave, L-452, Livermore, California, 94550.|UC Merced, School of Natural Sciences, Merced, California.
authors.forename: Aimy
authors.initials: A
authors.lastname: Sebastian
authors.affiliation: Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, 7000 East Ave, L-452, Livermore, California, 94550.
authors.forename: Deepa K
authors.initials: DK
authors.lastname: Murugesh
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hatsell
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York.
authors.forename: Aris N
authors.initials: AN
authors.lastname: Economides
authors.affiliation: Department of Orthopedic Surgery, UC Davis Medical Center, Sacramento, California.
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Christiansen
authors.affiliation: Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, 7000 East Ave, L-452, Livermore, California, 94550.|UC Merced, School of Natural Sciences, Merced, California.
authors.forename: Gabriela G
authors.initials: GG
authors.lastname: Loots
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008297:Male; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
keywords: ACL; RNA sequencing; osteoarthritis; tibial compression