Guinea pig osteoarthrosis : morphological and biochemical studies

Hartley guinea pigs spontaneously and reproducibly develop an arthropathy mimicking human primary osteoarthrosis. The morphological lesions first appear between 6 and 12 months of age, when it is confined to the non-meniscus-covered central compartment of the medial tibial plateau without initially involving the lateral side. The knees of these animals are constitutionally in varus position, so the load is mainly carried by the medial compartment and by its non-meniscus-covered parts in particular. An early change, while the cartilage surface is still intact, was a reduction in volume density of chondrocytes in the superficial zones. Cell clustering, hypertrophy and intensive staining of the extracellular matrix were found adjacent to areas of cartilage destruction, probably indicating reparative processes.

The concentration of proteoglycans in the articular cartilage was higher in areas presumably subjected to a higher load, and in healthy cartilage the concentration increased with age and body weight. The highest concentrations were found just before osteoarthrosis became morphologically evident, and the concentrations then decreased. Simultaneously, there was a reduction in collagen concentration and an increased content of tissue water.

Surgical redistribution of load by femur valgus osteotomy or unilateral tibia amputation altered the natural history of the arthropathy: osteotomy induced osteoarthrosis on the lateral condyle, while it reduced the changes on the medial side. Amputation did not completely prevent the development of fibrillation. After intervention, the extent of fibrillation was correlated to the proteoglycan concentration in the tissue.

Thus, the chondrocytes seem to modify the composition of the extracellular matrix to balance variations in load within a certain range. Hypothetically, with higher load, the rate of proteoglycan synthesis rise, thus increasing the swelling pressure of the tissue. After continued excessive load, the chondrocytes lost this ability. As a result of reduced proteoglycan concentration, the cartilage became less resistant to mechanical stress.

List of scientific papers

I. Wei L, de Bri E, Lundberg A, Svensson O (1998). Mechanical load and primary guinea pig osteoarthrosis. Acta Orthop Scand. Aug;69(4):351-7.
https://pubmed.ncbi.nlm.nih.gov/9798441

II. Wei L, Svensson O, Hjerpe A (1997). Correlation of morphologic and biochemical changes in the natural history of spontaneous osteoarthrosis in guinea pigs. Arthritis Rheum. Nov;40(11):2075-83.
https://pubmed.ncbi.nlm.nih.gov/9365098

III. Wei L, Svensson O, Hjerpe A (1998). Proteoglycan turnover during development of spontaneous osteoarthrosis in guinea pigs. Osteoarthritis Cartilage. 6(6):410-6.
https://pubmed.ncbi.nlm.nih.gov/10343774

IV. Wei L, Hjerpe A, Svensson O (1970). The effect of load on articular cartilage matrix and the development of osteoarthrosis. [Submitted]

V. Wei L, Hultenby K, Hjerpe A, Brismar H, Svensson O (1970). Distribution of chondroitin 4-sulfate epitopes (2/B/6) in spontaneous guinea pig osteoarthritis. [Submitted]