Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression
AbstractAnterior 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. View Full-Text
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Sebastian, A.; Chang, J.C.; Mendez, M.E.; Murugesh, D.K.; Hatsell, S.; Economides, A.N.; Christiansen, B.A.; Loots, G.G. Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression. Int. J. Mol. Sci. 2018, 19, 2657.
Sebastian A, Chang JC, Mendez ME, Murugesh DK, Hatsell S, Economides AN, Christiansen BA, Loots GG. Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression. International Journal of Molecular Sciences. 2018; 19(9):2657.Chicago/Turabian Style
Sebastian, Aimy; Chang, Jiun C.; Mendez, Melanie E.; Murugesh, Deepa K.; Hatsell, Sarah; Economides, Aris N.; Christiansen, Blaine A.; Loots, Gabriela G. 2018. "Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression." Int. J. Mol. Sci. 19, no. 9: 2657.
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