title: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1070, USA. Electronic address: ausstone@wakehealth.edu.
authors.forename: A V
authors.initials: AV
authors.lastname: Stone
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1070, USA. Electronic address: kvanderm@wakehealth.edu.
authors.forename: K S
authors.initials: KS
authors.lastname: Vanderman
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: jwilley@wakeheath.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Willey
authors.affiliation: Department of Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: dllong@wakehealth.edu.
authors.forename: D L
authors.initials: DL
authors.lastname: Long
authors.affiliation: Department of Pathology and Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: register@wakehealth.edu.
authors.forename: T C
authors.initials: TC
authors.lastname: Register
authors.affiliation: Department of Pathology and Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: cshively@wakehealth.edu.
authors.forename: C A
authors.initials: CA
authors.lastname: Shively
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: jstehle@wakehealth.edu.
authors.forename: J R
authors.initials: JR
authors.lastname: Stehle
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, University of North Carolina School of Medicine, 3300 Thurston Building, Campus Box 7280, Chapel Hill, NC 27599-7280, USA. Electronic address: richard_loeser@med.unc.edu.
authors.forename: R F
authors.initials: RF
authors.lastname: Loeser
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1070, USA. Electronic address: ferguson@wakehealth.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Ferguson
mesh_terms: D000367:Age Factors; D000818:Animals; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000378:metabolism; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015851:Interleukin-7; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D008592:Menisci, Tibial / Q000000981:diagnostic imaging / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000378:metabolism*; D011859:Radiography
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1
keywords: Aging; Chemokine; Cytokine; Meniscus; Osteoarthritis