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

Sebastian, Aimy; Chang, Jiun; Mendez, Melanie; Murugesh, Deepa; Hatsell, Sarah; Economides, Aris; Christiansen, Blaine; Loots, Gabriela

doi:10.3390/ijms19092657

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

Journal Article · Fri Sep 07 00:00:00 EDT 2018 · International Journal of Molecular Sciences (Online)

DOI:https://doi.org/10.3390/ijms19092657· OSTI ID:1476231

^[1]; Chang, Jiun ^[2]; Mendez, Melanie ^[2]; Murugesh, Deepa ^[1]; Hatsell, Sarah ^[3]; Economides, Aris ^[3]; Christiansen, Blaine ^[4]; Loots, Gabriela ^[2]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Directorate
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Directorate; Univ. of California, Merced, CA (United States). School of Natural Sciences
Regeneron Pharmaceuticals, Tarrytown, NY (United States)
UC Davis Medical Center, Sacramento, CA (United States). Dept. of Orthopedic Surgery

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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Univ. of California, Merced, CA (United States); UC Davis Medical Center, Sacramento, CA (United States)

Sponsoring Organization:: USDOE; USDOD; National Inst. of Health (NIH) (United States)

Grant/Contract Number:: AC52-07NA27344; OR130220; AR062603

OSTI ID:: 1476231

Report Number(s):: LLNL-JRNL-747404; 932332

Journal Information:: International Journal of Molecular Sciences (Online), Vol. 19, Issue 9; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 22 works

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Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice Sebastian, Aimy; Murugesh, Deepa K.; Mendez, Melanie E. International Journal of Molecular Sciences, Vol. 21, Issue 1 https://doi.org/10.3390/ijms21010364	journal	January 2020
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Title: Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression

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