Global molecular changes in a tibial compression induced ACL rupture model of post‐traumatic osteoarthritis

JC Chang, A Sebastian, DK Murugesh… - Journal of …, 2017 - Wiley Online Library
JC Chang, A Sebastian, DK Murugesh, S Hatsell, AN Economides, BA Christiansen
Journal of Orthopaedic Research, 2017Wiley Online Library
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 …
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.
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