Osteoarthritic changes in vervet monkey knees correlate with meniscus degradation and increased matrix metalloproteinase and cytokine secretion

• Published in: Osteoarthritis and cartilage Vol. 23; no. 10; pp. 1780 - 1789
• Main Authors: Stone, A.V, Vanderman, K.S, Willey, J.S, Long, D.L, Register, T.C, Shively, C.A, Stehle, J.R, Loeser, R.F, Ferguson, C.M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2015
• Subjects: Age Factors; Aging; Animals; Cartilage, Articular - diagnostic imaging; Cartilage, Articular - metabolism; Cercopithecus aethiops; Chemokine; Cytokine; Cytokines - metabolism; Female; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Interleukin-7; Knee Joint - diagnostic imaging; Knee Joint - metabolism; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 3 - metabolism; Matrix Metalloproteinase 8 - metabolism; Matrix Metalloproteinases, Secreted - metabolism; Menisci, Tibial - diagnostic imaging; Menisci, Tibial - metabolism; Meniscus; Osteoarthritis; Osteoarthritis, Knee - diagnostic imaging; Osteoarthritis, Knee - metabolism; Radiography; Rheumatology; Chemokine; Aging; Meniscus; Osteoarthritis; Cytokine
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2015.05.020

Summary Objective Meniscus injury increases osteoarthritis risk but its pathobiology in osteoarthritis is unclear. We hypothesized that older adult vervet monkeys would exhibit knee osteoarthritic changes and the degenerative menisci from these animals would secrete matrix metalloproteinases (MMPs) and pro-inflammatory cytokines that contribute to the development of osteoarthritis. Design In a cross sectional analysis of healthy young adult (9–12 years) and old (19–26 years) adult female vervet monkeys, knees were evaluated in vivo with computed tomography (CT) imaging, and joint tissues were morphologically graded at necropsy. Meniscus explants were subsequently cultured to evaluate meniscal MMP and cytokine secretion. Results CT images revealed significant bony osteoarthritic changes in 80% of older monkeys which included increases in osteophyte number and meniscal calcification. Meniscus and cartilage degradation scores were greater in the older monkeys and were positively correlated ( r  > 0.7). Menisci from older animals exhibiting osteoarthritic changes secreted significantly more MMP-1, MMP-3, and MMP-8 than healthy menisci from younger monkeys. Older menisci without significant osteoarthritic changes secreted more IL-7 than healthy young menisci while older osteoarthritic menisci secreted more IL-7 and granulocyte-macrophage colony-stimulating factor than healthy older menisci. Conclusions Aged vervets develop naturally occurring knee osteoarthritis that includes involvement of the meniscus. Degenerative menisci secreted markedly increased amounts of matrix-degrading enzymes and inflammatory cytokines. These factors would be expected to act on the meniscus tissue and local joint tissues and may ultimately promote osteoarthritis development. These finding also suggest vervet monkeys are a useful animal model for studying the progression of osteoarthritis.