Injury-induced joint degeneration accelerated in older animals

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 disease development. In a new study, researchers from LLNL, UC Merced, and UC Davis Medical Center examined age- and injury-related molecular changes in mouse knee joints that could contribute to OA. Using RNA sequencing, the scientists profiled the gene expression in the knee joints of 10-week-old, 62-week-old, and 95-week-old mice. They 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 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 (bony outgrowth associated with the degeneration of cartilage at the joint) formation compared with young mice. Although both age groups activated (or repressed) similar genes in response to injury, 62-week-old mice had higher activation of inflammatory cytokines (a type of protein associated with inflammatory signaling) 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 arthritis severity observed between these age groups.

[A. Sebastian, D.K. Murugesh, M.E. Mendez, N.R. Hum, N.D. Rios-Arce, J.L. McCool, B.A. Christiansen, and G.G. Loots, Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice, Int. J. Mol. Sci. 21(1), 364 (2020), doi: 10.3390/ijms21010364.]