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.; Hum, Nicholas R.; Rios-Arce, Naiomy D.; McCool, Jillian L.; Christiansen, Blaine A.; Loots, Gabriela G.

doi:10.3390/ijms21010364

Title: Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice

Journal Article · 05 January 2020 · International Journal of Molecular Sciences (Online)

DOI: https://doi.org/10.3390/ijms21010364 · OSTI ID:1581213

; Murugesh, Deepa K.; Mendez, Melanie E.;

; Rios-Arce, Naiomy D.; McCool, Jillian L.;

;

Aging and injury are two major risk factors for osteoarthritis (OA). Yet, very little is known about how aging and injury interact and contribute to OA pathogenesis. In the present study, we examined age- and injury-related molecular changes in mouse knee joints that could contribute to OA. Using RNA-seq, first we profiled the knee joint transcriptome of 10-week-old, 62-week-old, and 95-week-old mice and found that the expression of several inflammatory-response related genes increased as a result of aging, whereas the expression of several genes involved in cartilage metabolism decreased with age. To determine how aging impacts post-traumatic arthritis (PTOA) development, the right knee joints of 10-week-old and 62-week-old mice were injured using a non-invasive tibial compression injury model and injury-induced structural and molecular changes were assessed. At six-week post-injury, 62-week-old mice displayed significantly more cartilage degeneration and osteophyte formation compared with young mice. Although both age groups elicited similar transcriptional responses to injury, 62-week-old mice had higher activation of inflammatory cytokines than 10-week-old mice, whereas cartilage/bone metabolism genes had higher expression in 10-week-old mice, suggesting that the differential expression of these genes might contribute to the differences in PTOA severity observed between these age groups.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); US Dept. of Defense; USDOE; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1581213

Report Number(s):: LLNL-JRNL--797902; PII: ijms21010364

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Journal Issue: 1 Vol. 21; ISSN IJMCFK; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: Switzerland

Language:: English

References (44)

Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis Aigner, Thomas; Fundel, Katrin; Saas, Joachim Arthritis & Rheumatism, Vol. 54, Issue 11 https://doi.org/10.1002/art.22174	journal	November 2006
Loss of cartilage structure, stiffness, and frictional properties in mice lacking PRG4 Coles, Jeffrey M.; Zhang, Ling; Blum, Jason J. Arthritis & Rheumatism, Vol. 62, Issue 6 https://doi.org/10.1002/art.27436	journal	February 2010
Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice: Age-Related Gene Expression in OA Loeser, Richard F.; Olex, Amy L.; McNulty, Margaret A. Arthritis & Rheumatism, Vol. 64, Issue 3 https://doi.org/10.1002/art.33388	journal	February 2012
Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL/MpJ mice Lewis, John S.; Furman, Bridgette D.; Zeitler, Evan Arthritis & Rheumatism, Vol. 65, Issue 3 https://doi.org/10.1002/art.37796	journal	February 2013
Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor β-Responsive Genes in Osteoarthritis-Related Fibrosis: Elevated ECM Genes in OA-Related Synovial Fibrosis Remst, D. F. G.; Blom, A. B.; Vitters, E. L. Arthritis & Rheumatology, Vol. 66, Issue 3 https://doi.org/10.1002/art.38266	journal	February 2014
Identification of a Prg4 -Expressing Articular Cartilage Progenitor Cell Population in Mice : FATE-MAPPING OF Kozhemyakina, Elena; Zhang, Minjie; Ionescu, Andreia Arthritis & Rheumatology, Vol. 67, Issue 5 https://doi.org/10.1002/art.39030	journal	April 2015
Loss of Type I Collagen Telopeptide Lysyl Hydroxylation Causes Musculoskeletal Abnormalities in a Zebrafish Model of Bruck Syndrome: LOSS OF TYPE I COLLAGEN TELOPEPTIDE HYDROXYLATION IN ZEBRAFISH BS MODEL Gistelinck, Charlotte; Witten, Paul Eckhard; Huysseune, Ann Journal of Bone and Mineral Research, Vol. 31, Issue 11 https://doi.org/10.1002/jbmr.2977	journal	October 2016
SOST/Sclerostin Improves Posttraumatic Osteoarthritis and Inhibits MMP2/3 Expression After Injury: SOST OVEREXPRESSION IMPROVES PTOA OUTCOMES Chang, Jiun C.; Christiansen, Blaine A.; Murugesh, Deepa K. Journal of Bone and Mineral Research, Vol. 33, Issue 6 https://doi.org/10.1002/jbmr.3397	journal	April 2018
Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis: GLOBAL MOLECULAR CHANGES AFTER ACL INJURY Chang, Jiun C.; Sebastian, Aimy; Murugesh, Deepa K. Journal of Orthopaedic Research, Vol. 35, Issue 3 https://doi.org/10.1002/jor.23263	journal	May 2016
Using mouse models to investigate the pathophysiology, treatment, and prevention of post-traumatic osteoarthritis: MOUSE MODELS OF POST-TRAUMATIC OSTEOARTHRITIS Blaker, Carina L.; Clarke, Elizabeth C.; Little, Christopher B. Journal of Orthopaedic Research, Vol. 35, Issue 3 https://doi.org/10.1002/jor.23343	journal	June 2016
OP-1/BMP-7 in cartilage repair Chubinskaya, Susan; Hurtig, Mark; Rueger, David C. International Orthopaedics, Vol. 31, Issue 6 https://doi.org/10.1007/s00264-007-0423-9	journal	August 2007
BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells Zhou, Nian; Li, Qi; Lin, Xin Cell and Tissue Research, Vol. 366, Issue 1 https://doi.org/10.1007/s00441-016-2403-0	journal	April 2016
Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age Roos, Harald; Adalberth, Torsten; Dahlberg, Leif Osteoarthritis and Cartilage, Vol. 3, Issue 4 https://doi.org/10.1016/S1063-4584(05)80017-2	journal	December 1995
Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix Loeser, R. F. Osteoarthritis and Cartilage, Vol. 17, Issue 8 https://doi.org/10.1016/j.joca.2009.03.002	journal	August 2009
Low innate production of interleukin-1β and interleukin-6 is associated with the absence of osteoarthritis in old age Goekoop, R. J.; Kloppenburg, M.; Kroon, H. M. Osteoarthritis and Cartilage, Vol. 18, Issue 7 https://doi.org/10.1016/j.joca.2010.03.016	journal	July 2010
Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis Christiansen, B. A.; Anderson, M. J.; Lee, C. A. Osteoarthritis and Cartilage, Vol. 20, Issue 7 https://doi.org/10.1016/j.joca.2012.04.014	journal	July 2012
Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis Gardiner, M. D.; Vincent, T. L.; Driscoll, C. Osteoarthritis and Cartilage, Vol. 23, Issue 4 https://doi.org/10.1016/j.joca.2014.12.014	journal	April 2015
Aging-related inflammation in osteoarthritis Greene, M. A.; Loeser, R. F. Osteoarthritis and Cartilage, Vol. 23, Issue 11 https://doi.org/10.1016/j.joca.2015.01.008	journal	November 2015
Non-invasive mouse models of post-traumatic osteoarthritis Christiansen, B. A.; Guilak, F.; Lockwood, K. A. Osteoarthritis and Cartilage, Vol. 23, Issue 10 https://doi.org/10.1016/j.joca.2015.05.009	journal	October 2015
Perlecan is essential for cartilage and cephalic development Arikawa-Hirasawa, Eri; Watanabe, Hideto; Takami, Hiroya Nature Genetics, Vol. 23, Issue 3 https://doi.org/10.1038/15537	journal	November 1999
Mice lacking link protein develop dwarfism and craniofacial abnormalities Watanabe, Hideto; Yamada, Yoshihiko Nature Genetics, Vol. 21, Issue 2 https://doi.org/10.1038/6016	journal	February 1999
Sox9 is required for cartilage formation Bi, Weimin; Deng, Jian Min; Zhang, Zhaoping Nature Genetics, Vol. 22, Issue 1 https://doi.org/10.1038/8792	journal	May 1999
Normalization of RNA-seq data using factor analysis of control genes or samples Risso, Davide; Ngai, John; Speed, Terence P. Nature Biotechnology, Vol. 32, Issue 9 https://doi.org/10.1038/nbt.2931	journal	August 2014
Integrating single-cell transcriptomic data across different conditions, technologies, and species Butler, Andrew; Hoffman, Paul; Smibert, Peter Nature Biotechnology, Vol. 36, Issue 5 https://doi.org/10.1038/nbt.4096	journal	April 2018
Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease. Fassler, R.; Schnegelsberg, P. N.; Dausman, J. Proceedings of the National Academy of Sciences, Vol. 91, Issue 11 https://doi.org/10.1073/pnas.91.11.5070	journal	May 1994
Cytokine-like 1 Knock-out Mice ( Cytl1 −/− ) Show Normal Cartilage and Bone Development but Exhibit Augmented Osteoarthritic Cartilage Destruction Jeon, Jimin; Oh, Hwanhee; Lee, Gyusuk Journal of Biological Chemistry, Vol. 286, Issue 31 https://doi.org/10.1074/jbc.M111.218065	journal	June 2011
Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis Bernardo, Bianca C.; Belluoccio, Daniele; Rowley, Lynn Journal of Biological Chemistry, Vol. 286, Issue 43 https://doi.org/10.1074/jbc.M111.248039	journal	August 2011
Cytokine-like 1 (CYTL1) Regulates the Chondrogenesis of Mesenchymal Cells Kim, Jae-Sung; Ryoo, Zae Young; Chun, Jang-Soo Journal of Biological Chemistry, Vol. 282, Issue 40 https://doi.org/10.1074/jbc.M700965200	journal	July 2007
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Robinson, M. D.; McCarthy, D. J.; Smyth, G. K. Bioinformatics, Vol. 26, Issue 1 https://doi.org/10.1093/bioinformatics/btp616	journal	November 2009
STAR: ultrafast universal RNA-seq aligner Dobin, Alexander; Davis, Carrie A.; Schlesinger, Felix Bioinformatics, Vol. 29, Issue 1 https://doi.org/10.1093/bioinformatics/bts635	journal	October 2012
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features Liao, Y.; Smyth, G. K.; Shi, W. Bioinformatics, Vol. 30, Issue 7 https://doi.org/10.1093/bioinformatics/btt656	journal	November 2013
ToppGene Suite for gene list enrichment analysis and candidate gene prioritization Chen, J.; Bardes, E. E.; Aronow, B. J. Nucleic Acids Research, Vol. 37, Issue Web Server https://doi.org/10.1093/nar/gkp427	journal	May 2009
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks Shannon, P. Genome Research, Vol. 13, Issue 11 https://doi.org/10.1101/gr.1239303	journal	November 2003
The Long-term Consequence of Anterior Cruciate Ligament and Meniscus Injuries: Osteoarthritis Lohmander, L. Stefan; Englund, P. Martin; Dahl, Ludvig L. The American Journal of Sports Medicine, Vol. 35, Issue 10 https://doi.org/10.1177/0363546507307396	journal	October 2007
Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations Sokolove, Jeremy; Lepus, Christin M. Therapeutic Advances in Musculoskeletal Disease, Vol. 5, Issue 2 https://doi.org/10.1177/1759720X12467868	journal	January 2013
The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes Alquraini, Ali; Jamal, Maha; Zhang, Ling Arthritis Research & Therapy, Vol. 19, Issue 1 https://doi.org/10.1186/s13075-017-1301-5	journal	May 2017
Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study Boeth, Heide; Raffalt, Peter C.; MacMahon, Aoife Journal of Experimental Orthopaedics, Vol. 6, Issue 1 https://doi.org/10.1186/s40634-019-0179-3	journal	May 2019
Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis Surmann-Schmitt, C.; Widmann, N.; Dietz, U. Journal of Cell Science, Vol. 122, Issue 20 https://doi.org/10.1242/jcs.048926	journal	September 2009
The Skeletal Phenotype of Chondroadherin Deficient Mice Hessle, Lovisa; Stordalen, Gunhild A.; Wenglén, Christina PLoS ONE, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pone.0063080	journal	June 2013
Genes Involved in the Osteoarthritis Process Identified through Genome Wide Expression Analysis in Articular Cartilage; the RAAK Study Ramos, Yolande F. M.; den Hollander, Wouter; Bovée, Judith V. M. G. PLoS ONE, Vol. 9, Issue 7 https://doi.org/10.1371/journal.pone.0103056	journal	July 2014
Emerging drugs for osteoarthritis Matthews, Gloria L.; Hunter, David J. Expert Opinion on Emerging Drugs, Vol. 16, Issue 3 https://doi.org/10.1517/14728214.2011.576670	journal	May 2011
Roles of PLODs in Collagen Synthesis and Cancer Progression Qi, Yifei; Xu, Ren Frontiers in Cell and Developmental Biology, Vol. 6 https://doi.org/10.3389/fcell.2018.00066	journal	June 2018
Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression Sebastian, Aimy; Chang, Jiun; Mendez, Melanie International Journal of Molecular Sciences, Vol. 19, Issue 9 https://doi.org/10.3390/ijms19092657	journal	September 2018
Lysyl Oxidase-Like 2 Protects against Progressive and Aging Related Knee Joint Osteoarthritis in Mice Tashkandi, Mustafa; Ali, Faiza; Alsaqer, Saqer International Journal of Molecular Sciences, Vol. 20, Issue 19 https://doi.org/10.3390/ijms20194798	journal	September 2019

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60 APPLIED LIFE SCIENCES
PTOA
RNA-seq
aging
cartilage degeneration
chondrocytes
gene expression
osteoarthritis
scRNA-seq

Title: Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice

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