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Updated: Dec 31, 2025
Tissue Collection and RNA Extraction from the Human Osteoarthritic Knee Joint
Published on: July 22, 2021
Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development
Aimy Sebastian1, Deepa K Murugesh1, Melanie E Mendez1,2
1Physical and Life Sciences Directorate, Lawrence Livermore National Laboratories, Livermore, CA 94550, USA.
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.
Insights
Aging exacerbates osteoarthritis (OA) development after injury. Older mice show more severe cartilage damage and bone changes due to heightened inflammation and reduced cartilage repair mechanisms following injury.
Area of Science:
- Orthopedics
- Molecular Biology
- Gerontology
Background:
- Osteoarthritis (OA) is a degenerative joint disease influenced by aging and injury.
- The interplay between aging and injury in OA pathogenesis remains poorly understood.
- Investigating age-related molecular alterations is crucial for understanding OA development.
Purpose of the Study:
- To investigate age- and injury-related molecular changes in mouse knee joints contributing to OA.
- To compare the impact of injury on young versus aged mice in a post-traumatic arthritis (PTOA) model.
- To identify molecular mechanisms underlying differential PTOA severity in aging individuals.
Main Methods:
- RNA sequencing (RNA-seq) to profile knee joint transcriptomes in mice of different ages (10, 62, and 95 weeks).
- Non-invasive tibial compression injury model to induce post-traumatic arthritis (PTOA).
- Assessment of structural and molecular changes six weeks post-injury.
Main Results:
- Aging increased expression of inflammatory genes and decreased cartilage metabolism genes.
- Older mice (62 weeks) exhibited significantly more cartilage degeneration and osteophyte formation post-injury compared to younger mice.
- While transcriptional responses to injury were similar, older mice showed higher inflammatory cytokine activation and lower cartilage/bone metabolism gene expression.
Conclusions:
- Aging significantly worsens PTOA severity by promoting inflammation and impairing cartilage repair.
- Differential gene expression related to inflammation and metabolism in aging contributes to increased PTOA susceptibility.
- Understanding these age-related molecular changes is key to developing targeted OA therapies.
