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

Jiun C. Chang, Aimy Sebastian, Deepa K. Murugesh, Sarah Hatsell, Aris N. Economides, Blaine A Christiansen, Gabriela G. Loots

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - 2016

Keywords

  • ACL
  • Osteoarthritis
  • RNA sequencing
  • Tibial compression

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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