Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis)

Abstract

BackgroundThe aim of this study was to identify a primate model of degenerative knee osteoarthritis (KOA) that may be more relevant for research studies on degenerative KOA in humans.Material/MethodsSixteen specific-pathogen-free (SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A (n=8), an old group (22.0–25.3 years of age), and group B (n=8), a young group (3.0–5.2 years of age). For each primate, the behavior was observed, knee circumference was measured, knee joint X-rays were performed, and peripheral blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence (K-L) system was used for the classification of osteoarthritis. An enzyme-linked immunoassay (ELISA) was performed on knee joint fluid to measure levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using the Brittberg score and the Mankin histopathology grading score, respectively. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and the findings in the two groups of primates were compared.ResultsSeven old aged primates in group A were compared with group B, and showed significant differences in WBC count, synovial fluid IL-1β, TGF-β1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores (all, P<0.05).ConclusionsCynomolgus monkeys (Macaca fascicularis) might be a model for age-related degenerative KOA.

A New Method to Develop the Primate Model of Knee Osteoarthritis With Focal Cartilage Defect

“…Radiological results showed that the MHCD method increased the severity of articular cartilage injury, knee joint deformity, and subchondral bone damage, suggesting that the combined method promotes pathological damage to articular cartilage and accelerates OA progression. These changes are similar to those observed for human OA and are consistent with those in previous reports of surgically-induced OA in nonhuman primates ( Liu et al, 2018 ; Zhou et al, 2018 ). Furthermore, arthroscopic examination and gross morphological and cross-sectional analyses of articular surface wear suggested that pathologic degradation of the cartilage corresponded with radiographic results.…”

Society of Toxicologic Pathology Nonhuman Primate Special Interest Group: Idiopathic Femoral Head Chondrolysis in Nonclinical Research Macaques

“…2 Osteoarthritis is reported in macaques between the ages of 5 and 15 yr and commonly affects weight-bearing joints such as the knee. 10 While features of severe osteoarthritis such as articular cartilage fibrillation and osteophyte formation are similar to what was observed in many of our cases, osteoarthritis in young animals confined to a single joint would be uncommon. 2 Other conditions such as septic arthritis, rheumatoid arthritis, and traumatic injury would have characteristic clinicopathologic findings that would distinguish them from idiopathic femoral head chondrolysis.…”

Anatomical and Radiological Description of the &lt;i&gt;Macaca fascicularis&lt;/i&gt; Spine in Comparison with the Human Spine

“…This is also helpful in orthopedic research in the spine and knee. Importantly, following open knee surgeries and knee joint cartilage sampling, M. fascicularis have been demonstrated to be appropriate models for age-related knee osteoarthritis [6]. Anatomical findings that made M. fascicularis an appropriate model for knee osteoarthritis may also make it a fit for studies into degenerative diseases overall.…”