Comparative transcriptomics identifies novel genes and pathways involved in post-traumatic osteoarthritis development and progression

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Anterior cruciate ligament (ACL) injuries often result in post-traumatic osteoarthritis (PTOA). To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced transcriptional changes in knee joints of three mouse strains with varying susceptibility to OA: STR/ort (highly susceptible), C57BL/6J (moderately susceptible) and super-healer MRL/MpJ (not susceptible). Right knee joints of the mice were injured using a non-invasive tibial compression injury model and global gene expression was quantified before and at 1-day, 1-week, and 2-weeks post-injury using RNA-seq. Following injury, injured and uninjured joints of STR/ort and injured C57BL/6J joints displayed significant cartilage degeneration while MRL/MpJ had little cartilage damage. Gene expression analysis suggested that prolonged inflammation and elevated catabolic activity in STR/ort injured joints, compared to the other two strains may be responsible for the severe PTOA phenotype observed in this strain. MRL/MpJ had the lowest expression values for several inflammatory cytokines and catabolic enzymes activated in response to ACL injury. Furthermore, we identified several genes highly expressed in MRL/MpJ compared to the other two strains including B4galnt2 and Tpsab1 which may contribute to enhanced healing in the MRL/MpJ. Overall, this study has increased our knowledge of early molecular changes associated with PTOA development.

Original languageEnglish (US)
Article number2657
JournalInternational Journal of Molecular Sciences
Volume19
Issue number9
DOIs
StatePublished - Sep 7 2018

Keywords

  • ACL injury
  • B4galnt2
  • C57BL/6J
  • Inflammation
  • MRL/MpJ
  • Osteoarthritis
  • PTOA
  • Regeneration
  • RNA-seq
  • STR/ort

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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