Laboratory Animal Science Copyright 1997 by the American Association for Laboratory Animal Science Vol 47, No 6 December 1997 598 Osteoarthritis (OA) is a degenerative disease of the ar- ticular joints characterized by focal areas of cartilage fi- brillation, articular cartilage hypertrophy, bony changes, and eventual destruction of the articular surface. These changes result in pain and loss of joint mobility (1). Preva- lence of OA increases with age and other predisposing fac- tors, including knee injury and obesity (2, 3). Several sur- gically induced models of OA in Dunkin Hartley guinea pigs have been described (4–6). Animal models of sponta- neous OA, such as the Hartley guinea pig, that develop lesions resembling those of human OA are used to study the etiopathogenesis of the disease (7). The Dunkin Hartley guinea pig develops age-related, spontaneous OA of the knee and other joints (8). Previous studies have indicated that at the age of 3 months, guinea pigs develop mild OA detected by presence of minimal histologic changes. The disease progresses, and by 16 to 18 months of age, moder- ate to severe cartilage degeneration on the medial tibial plateau has been described (8, 9). Guinea pigs have also been used in creating surgically induced OA, including partial medial meniscectomy of the femorotibial joints. In contrast to that of human OA, the onset and progression of the disease in these surgical models occurs at a rapid rate (10–12). We describe the radiographic and histologic char- Spontaneous Osteoarthritis in Dunkin Hartley Guinea Pigs: Histologic, Radiologic, and Biochemical Changes Pablo A. Jimenez,* Sonya S. Glasson, Olga V. Trubetskoy, and Howard B. Haimes Abstract | Dunkin Hartley guinea pigs develop spontaneous, age-related osteoarthritis (OA) of the knee and other joints. Histologic changes are observed beginning at 3 months of age. Disease severity increases with age, and at 18 months moderate to severe OA is observed. A study was undertaken to assess the morpho- logic and biochemical changes of 22-month-old animals, and to compare them with values in 2-month-old guinea pigs. Biochemical indices characteristic of OA, from tibial cartilage, indicated an increase in proteoglycan content from 233 2 g/mg (mean SEM) at 2 months of age to 365 6 g/mg at 22 months. Collagen concentration in cartilage decreased from 364 2 g/mg at 2 months to 223 3 g/mg at 22 months. Proteoglycan fragments found in synovial fluid measured 4.6 1 g/ml at 2 months and increased to 37 2 g/ ml at 22 months. Radiographic changes observed at 22 months included marginal osteophytes of the tibia and femur, sclerosis of the subchondral bone of the tibial plateau, femoral condyle cysts, and calcification of the collateral ligaments. Histologic evaluation revealed severe OA, with a Mankin score of 10.7 0.5 in 22-month- old animals. In contrast, 2-month-old animals had no histologic or radiographically detectable lesions. The results of the study reported here indicate that the lesions observed in this model are similar to those of human OA. Spontaneous development of OA in guinea pigs is amenable to the study of the pathogenesis of OA and to the evaluation of potential disease-modifying agents. OsteoArthritis Sciences, Inc., Cambridge, Massachusetts *Address correspondence to Dr. Pablo A. Jimenez, Human Genome Sciences, Inc., 9410 Key West Avenue, Rockville, MD 20850. acteristics of guinea pig articular cartilage at 2 and 22 months of age. In addition, we describe qualitative and quantitative biochemical indices in synovial fluid. These indices reflect aspects of cartilage proliferation and degen- eration, and may be useful to monitor disease progression or to evaluate potential therapeutic, disease-modifying agents. Materials and Methods Animals: Male Dunkin Hartley guinea pigs were ob- tained at 2 (n = 8) and 22 (n = 14) months of age from Charles River Laboratories (Wilmington, Mass.). Animals were group housed in 29 x 21 x 10-in (width x depth x height) plastic cages (Allentown Caging Equipment, Allen- town, N.J.). Food (Guinea Pig Chow no. 5025; Ralston Purina, Richmond, Ind.) and water were available ad libi- tum. Animals were euthanized by administration of lethal doses of pentobarbital (300 mg/kg of body weight, given intraperitoneally). This study was conducted according to the guidelines set forth by the OsteoArthritis Sciences, Inc., Institutional Animal Care Committee, which reviewed and approved the experimental protocol. Animal housing, care, and procedures were in accordance with the NIH ILAR Guide. Analysis of cartilage and synovial fluid: Cartilage was harvested from the entire surface of the medial tibial plateau, using a Meyer-Hoffer 1.5-mm microdissecting curette (Roboz Surgical Instruments, Rockville, Md.), then