Osteoarthritis In Guinea Pig Research Articles

Early alterations in the collagen meshwork and lesions in the ankles are associated with spontaneous osteoarthritis in guinea-pigs

Objective The purpose of this study was to evaluate matrix changes in knee cartilage prior to development of surface disruptions and to examine the ankle for evidence of osteoarthritis (OA)-like lesions. Design Guinea-pig ankles and knees were examined histologically or viewed with polarization microscopy to reveal changes in orientation of the collagen fibers. Results The medial femoral condyles were virtually free of histologic changes at 3 months of age. Changes were present by 6 months. Medial tibial plateau histologic changes were seen at 3 months which became more pronounced with age. Alterations in the collagen meshwork corresponding to areas of proteoglycan (PG) loss were noted in animals with an intact articular surface as early as 3 months. Histologic changes were noted in the ankles as early as 3 months of age which included surface disruptions, cell loss and loss of PG staining. Only knee joint composite histology scores were significantly elevated at 3 months while both knee and ankle scores were significantly elevated at 6 months. Knee and ankle joint scores were not different from each other at 6 months. Conclusions Alterations in the orientation of the collagen network of the cartilage correlated with Safranin-O loss suggesting that alterations in collagen:PG interactions play a role in the early phases of the OA process and precede frank histologic changes in the articular surface. The results in this study report for the first time OA-like lesions occurring spontaneously in articular cartilage of the ankle in the guinea-pig. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

Effect of load on articular cartilage matrix and the development of guinea-pig osteoarthritis

Objective To study the biochemical changes in the early development of primary guinea-pig knee osteoarthritis (OA) and its dependence on load.Methods Load distribution was modified with below-knee amputation or femur valgus osteotomy in 9-month-old guinea-pigs. Soft tissue sham operated animals served as controls. The composition of uncalcified and calcified articular cartilage at the medial and lateral tibial condyle was studied by analysing small and large proteoglycans (PG) by gel electrophoresis and sulfation pattern with high-performance liquid chromatography. Collagen concentration was also determined.Results The articular surfaces with a presumed higher load after surgery had a slight, but consistent, higher water content. Decreased load—on the ipsilateral medial condyle after femur osteotomy, and on the ipsilateral medial and lateral condyles following tibia amputation—was associated with an increased concentration of PGs, while this concentration decreased in condyles with increased load. Collagen concentration followed a similar pattern in the osteotomy group. In the amputated animals collagen concentration went down in all condyles, regardless of change of load. The aggregability and proportion of large and small PGs, the concentration of hyaluronan and the sulfation pattern of chondroitin sulfate was not affected by load. No consistent changes in PG, collagen or HA concentration, HA aggregability or sulfation pattern were seen in the calcified cartilage.Conclusions Primary guinea-pig knee OA is a reproducible model similar to human OA. It develops slowly and biochemical changes seem to appear before the morphological lesions become evident. The biochemical events are affected by load redistribution and correlate closely to morphological changes. These changes eventually result in a cartilage devoid in aggrecan, as also has been demonstrated in advanced human OA. All of this makes primary guinea-pig OA a suitable model for studying early OA changes.

Effect of an inhibitor of matrix metalloproteinases on spontaneous osteoarthritis in guinea pigs.

Recently discovered chemically modified tetracyclines have been found to be effective inhibitors of matrix metalloproteinase (MMP)-mediated connective tissue destruction in a variety of pathologic processes, including rheumatoid arthritis and osteoarthritis (OA). Since the histologic techniques used in our laboratory have been validated in Hartley guinea pigs, which have a high incidence of OA-like changes in the proximal tibia, we have used two tetracyclines which have potent inhibitory capacity against various MMPs, doxycycline (Dox) and a compound known as chemically modified tetracyclines (CMT-7). These were given by mouth to a group of guinea pigs for 4 to 8 months, and we assessed the effect of the compound on morphologic and biochemical aspects of OA. We found that prophylactic CMT-7 given orally decreases OA changes in the knee joints both in vitro and in vivo in the guinea pig OA model. Cartilage fibrillation and destruction, in addition to subchondral bone sclerosis and cyst formation, were all decreased in the central compartment of the medial condyle, which is most affected by OA compared with controls. Also collagen, hyaluronan and proteoglycancontent in cartilage was higher in the CMT-7 treated group compared with controls. In contrast, OA changes were not decreased in the Dox group. Our results confirm that various tetracyclines have reduced the severity of OA in animal models, indicating the therapeutic potential of this class of compounds in the future.

Ultrastructural changes in primary guinea pig osteoarthritis with special reference to collagen.

Collagen fibril distribution and surface and volume densities in proximal tibial articular cartilage were measured in 6- and 12-month-old Dunkin-Hartley guinea pigs developing primary osteoarthritis. At 12 months, gross fibrillation and ulceration of the articular cartilage were observed on the medial but not on the lateral condyle. Collagen volume density decreased with age in the interterritorial compartments in the superficial zone, medially by 16% and laterally by 8%. In the upper radial zone, collagen volume density decreased interterritorially by 10% on the medial condyle only. Despite gross osteoarthritic changes, only moderate and predominantly focal ultrastructural collagen changes were observed. Thus neither gross network disruption nor fibril thickening seems to be a general feature in early guinea pig osteoarthritis.

Induction of osteoarthritis in guinea pigs by transection of the anterior cruciate ligament: Radiographic and histopathological changes

Osteoarthritis (OA) is characterized by degenerative 13 lesions in articular cartilage leading to exposed subchondral bone and hyper t rophic changes such as osteophytes. 12 A number o f models have been established [1]. Induc t ion 11 of OA has been augmented by joint instability, ,-. 10 immobil izat ion or in t roduct ion o f foreign substances 9 into the joint [2]. Surgically induced models include ~ 8 partial menisectomy in rabbit [3] and guinea pig [4], ~a 7 anterior cruciate l igament transection (ACL) in dog [5] and gluteal resection in guinea pig [6]. The model ~ 6 rll presented here, displays histopathologic, ana tomic and .= 5 radiologic features o f the h u m a n disease. -~ 4

Bone sialoprotein distribution in guinea pig osteoarthritis

Morphological studies of osteoarthritis (OA) have largely been performed on surgical specimens from patients with advanced disease. Such specimens do not allow conclusions on the early events of OA and consequently little is known about initiating agents and pathogenetic mechanisms. To overcome these obstacles, various animal models have been designed. Most of these models, however, involve an intraarticular intervention resulting in rapidly progressive changes, quite unlike primary osteoarthrosis. There are, however, naturally occurring OA-like conditions in animals, e.g. Dunkin Hartley guinea pigs. In a recent study we have presented quantitative data on articular cartilage and subchondral bone during development of guinea pig OA. Previous studies have shown that bone changes are important in the OA pathogenesis (Radin 1986).

Effects of Body Weight Restriction on the Development and Progression of Spontaneous Osteoarthritis in Guinea Pigs

Hartley albino guinea pigs develop spontaneous osteoarthritis (OA) of the knee joint. A study was done to determine the importance of body weight in the pathogenesis of this disease. Two groups of 20 male guinea pigs each were maintained on the same diets. The control group was allowed ad libitum feed consumption and the other group was restricted to 30-35 gm of feed per day. Ten animals from each group were killed at 9 months of age to evaluate histologic features of the knee joints. The severity of the OA lesions was reduced by 40%, in conjunction with a 28% decrease in body weight, in the diet-restricted group. The remaining animals were killed at 18 months of age. Those in the diet-restricted group had a 56% reduction in severity of lesions, with a 29% decrease in body weight. These results indicate that body mass in guinea pigs, as in humans, is an important predisposing factor for the development of spontaneous OA of the knee.

Experimentally induced osteoarthritis in guinea pigs: metabolic responses in articular cartilage to developing pathology.

Developing osteoarthritis, surgically induced in the right hind knee joint of guinea pigs by different procedures (A or B), was studied in animals maintained on either minimal or supplemented levels of dietary vitamin C. Procedure A, consisting of transecting the anterior cruciate and major portion of the medial collateral ligaments, resulted in a slower developing and less severe form of the disease than procedure B which also included a partial menisectomy. Regardless of the surgical procedure used, animals on minimal levels of ascorbate always exhibited more severe pathology than those on high levels. When compared with controls, a significant enhancement of acid phosphatase characterized arthritic cartilage in both supplemented and minimal diet groups, although the increase was 2-fold greater in the latter. In addition, a significant elevation of arylsulfatase A and B activities was observed only in the minimal diet group. Early stages of pathology in both diet groups were characterized by formation of repair cartilage which stained strongly with Safranin O on histologic sections. As the disease progressed, pitting, ulcerations, and eburnation occurred in the minimal diet group. Cartilage weight in normal joints was greater for guinea pigs kept on high levels of vitamin C. It is likely that this stimulated synthesis of cartilage in the supplemented animals protected against the erosion of the articular cartilage which characterized the more severe disease process in the guinea pigs on minimal levels of ascorbate.

Natural history of degenerative joint disease in small laboratory animals. 5. Osteoarthritis in guinea pigs.

AbstractThe naturally occurring osteoarthritis of guinea pigs is described. Osteophyte formation was observed both in the presence and absence of erosion of the articular cortex. Weight bearing was not considered the sole cause of the degenerative changes observed in guinea pig joints.Es describite le occurrentia natural de osteoarthritis in porcos de India. Formationes osteophytic esseva observate in le presentia e in le absentia de erosion del cortice articular. Le carga del peso supportate non esseva considerate como le causa unic del alterationes degeneratori observate in articulationes de porcos de India.