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Int. J. Mol. Sci. 2018, 19(9), 2657; https://doi.org/10.3390/ijms19092657

Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression

1
Physical and Life Sciences Directorate, Lawrence Livermore National Laboratories, Livermore, CA 95101, USA
2
School of Natural Sciences, UC Merced, Merced, CA 95101, USA
3
Regeneron Pharmaceuticals, Tarrytown, NY 10020, USA
4
Department of Orthopedic Surgery, UC Davis Medical Center, Sacramento, CA 95101, USA
*
Author to whom correspondence should be addressed.
Received: 14 August 2018 / Revised: 1 September 2018 / Accepted: 1 September 2018 / Published: 7 September 2018
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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. View Full-Text
Keywords: osteoarthritis; RNA-seq; STR/ort; C57BL/6J; MRL/MpJ; ACL injury; PTOA; regeneration; inflammation; B4galnt2 osteoarthritis; RNA-seq; STR/ort; C57BL/6J; MRL/MpJ; ACL injury; PTOA; regeneration; inflammation; B4galnt2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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.

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