The commercial pig as a model of spontaneously-occurring osteoarthritis (original) (raw)
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Laboratory animal science, 1997
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 morphologic 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 micrograms/mg (mean +/- SEM) at 2 months of age to 365 +/- 6 micrograms/mg at 22 months. Collagen concentration in cartilage decreased from 364 +/- 2 micrograms/mg at 2 months to 223 +/- 3 micrograms/mg at 22 months. Proteoglycan fragments found in synovial fluid measured 4.6 +/- 1 micrograms/ml at 2 months and increased to 37 +/- 2 micrograms/ml at 22 months. Radiographic changes observed at 22 months included marginal osteophytes of the tibia and...
Proteoglycan turnover during development of spontaneous osteoarthrosis in guinea pigs
Osteoarthritis and Cartilage, 1998
The study was performed to clarify the metabolic background of the variations in proteoglycan concentrations, relating to ageing and the spontaneous development of osteoarthrosis in guinea pigs. Six-, 9- and 12-month-old Hartley guinea pigs were injected intraperitoneally with Na2(35)SO4. The incorporation and degradation of various proteoglycans were analyzed in different areas of tibial articular cartilage during the development of osteoarthrosis. Proteoglycan synthesis was most active in the uncalcified cartilage of 6-month animals and highest in the medial compartment with its presumably higher load. The breakdown of proteoglycans decreased with age. The onset of osteoarthrosis was associated with decreased synthesis of large and small proteoglycans, while the rate of degradation remained unchanged. During onset of osteoarthrosis the synthesis of large proteoglycans gradually becomes insufficient to compensate for the simultaneous degradation. This differs from findings in more rapidly progressing, experimental secondary osteoarthrosis, where a substantial increase in the rate of degradation is more conspicuous.
Osteoarthritis and Cartilage, 2002
Objective: To evaluate the interaction of bone and cartilage in knee osteoarthritis (OA) pathogenesis in two guinea-pig strains with appreciable differences in bone metabolism. Design: Two guinea-pig strains were evaluated for their susceptibilities to OA using semi-quantitative histological grading of knee joints and quantification of biomarkers including urinary excretion of hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) collagen cross-links, serum osteocalcin (OC), and synovial fluid levels of keratan sulfate (KS). Results: At 12 months of age, Strain 13 guinea-pigs had minimal to mild histological evidence of OA compared to the Hartley strain guinea-pigs. The Hartley strain, with more severe OA, had a higher rate of bone formation (serum osteocalcin) and bone resorption (HP and LP) evident at a young age with persistence of a greater rate of bone formation at 12 months of age. The Strain 13 possessed much thicker subchondral bone at the outset (2 months) compared to the Hartley; however, the Hartley strain showed the greatest increase in subchondral bone thickness coincident with the development of cartilage degeneration. Thus, the process of subchondral bone thickening, in contrast to the absolute initial subchondral bone thickness, was a hallmark of OA in the guinea-pig. Moreover, Strain 13 had lower intraarticular proteoglycan turnover. Levels of synovial fluid keratan sulfate were positively correlated with the severity of histological OA. Conclusions: This pilot study represents the first evidence of differential susceptibility to OA in guinea-pigs. Comparison of these two strains of guinea-pig has revealed that increased metabolism within the affected tissues, cartilage and bone, is associated with the development and progression of OA. This work demonstrates that the Strain 13 is a viable age-matched control to the Hartley strain and merits a more in depth evaluation of the contribution of bone and bone metabolism to OA.
Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants
Equine Veterinary Journal
Background: Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. Objectives: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1β and cartilage explants with mild osteoarthritis. Study design: In vitro experimental study. Methods: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1β and IL-1 receptor antagonist (IL-1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL-1β prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase-13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6 and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage. Results: The IL-1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation-and cartilage matrix degradation-related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h-and PCStreated pellets versus untreated controls. Growth factor signalling genes were upregulated-FGF7 in all treatment groups, BMP2 in PS24h-, and INHBA in PCStreated-compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups. Main limitations: Results from in vitro models cannot be directly translated to in vivo situations.
Arthritis research & therapy, 2005
Osteoarthritis (OA), the commonest form of arthritis and a major cause of morbidity, is characterized by progressive degeneration of the articular cartilage. Along with increased production and activation of degradative enzymes, altered synthesis of cartilage matrix molecules and growth factors by resident chondrocytes is believed to play a central role in this pathological process. We used an ovine meniscectomy model of OA to evaluate changes in chondrocyte expression of types I, II and III collagen; aggrecan; the small leucine-rich proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming growth factor-beta; and connective tissue growth factor. Changes were evaluated separately in the medial and lateral tibial plateaux, and were confirmed for selected molecules using immunohistochemistry and Western blotting. Significant changes in mRNA levels were confined to the lateral compartment, where active cartilage degeneration was observed. In this region there was ...
Cartilage proteoglycans from normal and osteochondrotic porcine joints
Canadian journal of comparative medicine. Revue canadienne de médecine comparée, 1985
Modern pigs grow fast but are highly susceptible to degenerative joint abnormalities, including osteochondrosis. Normal and osteochondrotic humeri and femurs were obtained from five normal and ten lame adolescent boars to study cartilage proteoglycans. Histological examination of joints indicated a locally-reduced intensity of proteoglycan staining by safranin-O in lesion areas of cartilage. Cartilage proteoglycans extracted with 4.0 M guanidinium chloride were studied using Sepharose 2B gel chromatography. The proteoglycans from severely osteochondrotic joints were less (P less than 0.05) aggregated and contained a greater (P less than 0.05) proportion of smaller monomers than those from normal joints. Loss or damage of core protein, including its hyaluronic acid-binding regions, may account for the greater proportion of small monomers. The results also indicated that the proportion of hyaluronic acid in the total glycosaminoglycan uronic acid fraction, estimated by Sephadex G-200 ...