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

Abstract

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.

Traumatic and Degenerative Meniscus Tears Have Different Gene Expression Signatures

“…The expression of MMP1 and MMP3 has also been shown to be elevated in the synovial fluid of patients with OA 24 . A recent animal study demonstrated elevated expression of MMP1 and MMP3 from the menisci of knees with OA compared to menisci from knee without OA 26 . However, MMP3 expression was lower in the meniscus of human patients with OA compared to controls 20 , which is congruent with our findings that traumatic meniscus tears have elevated MMP-3 compared to degenerative meniscus tears.…”

Gene-expression changes in knee-joint tissues with aging and menopause: implications for the joint as an organ

“… 20 Although not evaluated in human meniscus with aging, nonhuman primate meniscus-explant cultures exhibited increased MMP1 and MMP3 in older degenerated versus younger healthy menisci. 21 With menopause, FC AC, TP AC, and MM exhibited no changes in MMPs and TIMPs, but LM exhibited decreases in TIMPs. In AC, collagen was decreased (TP AC), but proteoglycans were increased (FC AC and TP AC).…”

Running decreases knee intra-articular cytokine and cartilage oligomeric matrix concentrations: a pilot study

“…One of the most remarkable findings of the present study was the decrease in concentration of the cytokine GM-CSF in knee joint synovial fluid of all subjects following the run. This result is particularly interesting because synovial fluid GM-CSF is known to be significantly elevated in cases of knee OA and rheumatoid arthritis (RA) (Cameron et al 1997;Arend and Dayer 1990), as well as in cases of knee injury that precede knee OA (Stone et al 2015). Further, it is believed that neutralization of GM-CSF might effectively control OA pain and progression (Cook et al 2012).…”