Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice
Abstract
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.
- Publication Date:
- Research Org.:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program; US Dept. of Defense; National Institutes of Health (NIH)
- OSTI Identifier:
- 1581213
- Alternate Identifier(s):
- OSTI ID: 1662044
- Report Number(s):
- LLNL-JRNL-797902
Journal ID: ISSN 1422-0067; IJMCFK; PII: ijms21010364
- Grant/Contract Number:
- 20-LW-002 and 16-ERD-007; AC52-07NA27344; 20-LW-002; 16-ERD-007; R01 AR075013; PR180268/P1
- Resource Type:
- Published Article
- Journal Name:
- International Journal of Molecular Sciences (Online)
- Additional Journal Information:
- Journal Name: International Journal of Molecular Sciences (Online) Journal Volume: 21 Journal Issue: 1; Journal ID: ISSN 1422-0067
- Publisher:
- MDPI
- Country of Publication:
- Switzerland
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; osteoarthritis; aging; PTOA; gene expression; RNA-seq; cartilage degeneration; scRNA-seq; chondrocytes
Citation Formats
Sebastian, Aimy, Murugesh, Deepa K., Mendez, Melanie E., Hum, Nicholas R., Rios-Arce, Naiomy D., McCool, Jillian L., Christiansen, Blaine A., and Loots, Gabriela G. Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice. Switzerland: N. p., 2020.
Web. doi:10.3390/ijms21010364.
Sebastian, Aimy, Murugesh, Deepa K., Mendez, Melanie E., Hum, Nicholas R., Rios-Arce, Naiomy D., McCool, Jillian L., Christiansen, Blaine A., & Loots, Gabriela G. Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice. Switzerland. https://doi.org/10.3390/ijms21010364
Sebastian, Aimy, Murugesh, Deepa K., Mendez, Melanie E., Hum, Nicholas R., Rios-Arce, Naiomy D., McCool, Jillian L., Christiansen, Blaine A., and Loots, Gabriela G. Mon .
"Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice". Switzerland. https://doi.org/10.3390/ijms21010364.
@article{osti_1581213,
title = {Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice},
author = {Sebastian, Aimy and Murugesh, Deepa K. and Mendez, Melanie E. and Hum, Nicholas R. and Rios-Arce, Naiomy D. and McCool, Jillian L. and Christiansen, Blaine A. and Loots, Gabriela G.},
abstractNote = {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.},
doi = {10.3390/ijms21010364},
journal = {International Journal of Molecular Sciences (Online)},
number = 1,
volume = 21,
place = {Switzerland},
year = {Mon Jan 06 00:00:00 EST 2020},
month = {Mon Jan 06 00:00:00 EST 2020}
}
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Cited by: 15 works
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Figures / Tables:
Figure 1: Age-related changes in the knee joint gene expression. Genes up- (A) and down-regulated (B) in 62-week-old (62W) mice and 95-week-old (95W) mice compared with 10-week-old (10W) mice and in 95-week-old mice compared with 62-week-old mice. (C) Inflammatory response-related genes up-regulated in both 62-week-old and 95-week-old compared with 10-week-oldmore »
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