1. Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression.
- Author
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Sebastian, Aimy, Chang, Jiun C, Mendez, Melanie E, Murugesh, Deepa K, Hatsell, Sarah, Economides, Aris N, Christiansen, Blaine A, and Loots, Gabriela G
- Subjects
Cartilage ,Articular ,Animals ,Mice ,Inbred C57BL ,Osteoarthritis ,Disease Progression ,Metalloproteases ,Cytokines ,Up-Regulation ,Transcriptome ,Anterior Cruciate Ligament Injuries ,ACL injury ,B4galnt2 ,C57BL/6J ,MRL/MpJ ,PTOA ,RNA-seq ,STR/ort ,inflammation ,osteoarthritis ,regeneration ,Cartilage ,Articular ,Mice ,Inbred C57BL ,Other Chemical Sciences ,Genetics ,Other Biological Sciences ,Chemical Physics - 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.
- Published
- 2018