An experimental model of osteoarthritis; early morphological and biochemical changes

237

150

Objective. To evaluate the sequence of changes in articular cartilage, trabecular bone, and subchondral plate in dogs with osteoarthritis (OA), 3 months, 18 months, and 54 months after anterior cruciate ligament transection (ACLT).Methods. Specimens of the medial tibial plateau Submitted for publication May 5 , 1992; accepted in revised form February 9, 1993. were analyzed with microscopic computed tomography (micro-CT) at a resolution of 60 pm, and biochemical and morphologic changes in the femoral articular cartilage were assessed.Results. At 3 months and 18 months after ACLT, the articular cartilage in the unstable knee showed histologic changes typical of early OA and increased water content and uronic acid concentration; by 54 months, full-thickness ulceration had developed. Micro-CT analysis showed a loss of trabecular bone in the unstable knee, compared with the contralateral knee, at all time points. Al. both 18 and 54 months, the differences in trabecular thickness and surface-tovolume ratio were greater than at 3 months. Although the mean subchondral plale thickness, especially in the medial aspect of the medial tibial plateau, was greater in the OA knee than in the contralateral knee 18 months and 54 months after ACLI', these differences were not statistically significant; however, the difference was significantly greater at 54 months than at 3 months.Conclusion. Thickening of the subchondral bone is not required for the development of cartilage changes of OA in this model. The bony changes that develop after ACLT, however, could result in abnormal transmission of stress to the overlying cartilage and thereby contribute to the progression of cartilage degeneration.In the pathogenesis of osteoarthritis (OA), interactions among all the major joint tissues, including the articular cartilage, synovium, and subchondral bone, have been implicated (1). While a large body of work has focused on the alterations in the articular cartilage in OA in humans and experimental animal

Section: Resultssupporting

confidence: 87%

A longitudinal study of subchondral plate and trabecular bone in cruciate‐deficient dogs with osteoarthritis followed up for 54 months

Dedrick

Goldstein

Brandt

et al. 1993

237

150

“…Ultrastructural data confirmed the loss of a defined and graded organization in the fibrillar and proteoglycan components of the chondron (Figures 5A and C), and are consistent with previous descriptions of enlarged lacunae in the initial stages of spontaneous (29,30,51,52) and experimental (24,26,31,33,53) OA. Further evidence suggests that destruction of the ''pericellular lacunar walls" in osteoarthritic cartilage (25) and increased collagenolytic breakdown of the ''pericellular or perilacunar region" in the Pond-Nuki dog model of OA (33) represent the first morphologically identifiable features of degenerative change.…”

Section: Discussionsupporting

confidence: 91%

“…The histologic results presented are consistent with those found in numerous studies of human and experimental OA (20)(21)(22)(23)(24)(25)(26)(27). They show a general loss of intercellular matrix staining, but persistence of a strong pericellular reaction around most chondrocytes and cell clusters.…”

Section: Discussionsupporting

confidence: 89%

“…It is characterized in both spontaneous and experimentally induced disease by marked alterations in matrix histochemistry (20)(21)(22)(23)(24)(25)(26)(27) and ultrastructure (28-34), biochemical composition (3541), and cellular metabolism (21,35,(42)(43)(44). Variable rates of chondrocyte necrosis and reactive mitotic proliferation have also been reported (35,(45)(46)(47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage

Poole

Matsuoka

Schofield

1991

Chondrons were isolated from human and canine osteoarthritic cartilage using low-speed homogenization techniques. Changes in chondron morphology were evaluated using differential interference-contrast microscopy, phase-contrast microscopy, and histochemical and ultrastructural methods. Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography. The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters. These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.Chondrocytes from hyaline cartilage are surrounded by a specialized microenvironment termed the chondron (1-3). In ultrastructural studies of mature canine and human articular cartilage, chondrons in the middle and deep layers were shown to consist of a single chondrocyte, a pericellular matrix rich in proteoglycans, and a pericellular capsule containing

“…Only a relatively small amount of enzyme is likely to be present in joint cartilage in such a chronic and slowly developing disorder as osteoarthritis. This could produce the large but submonomeric size proteoglycan fragments that had been observed by some researchers in experimentally produced osteoarthritis cartilage (22). Ehrlich et a1 (23) obtained an enzyme preparation from human osteoarthritic articular cartilage fresh from surgery.…”

Section: Discussionmentioning

confidence: 99%

Further characterization of a neutral metalloprotease isolated from human articular cartilage

Sapolsky

Howell

1982

The neutral metalloprotease extracted from 1,200 gm of human articular cartilage was purified 1,400‐ to 2,400‐fold by diethylaminoethyl‐ and carboxymethyl‐Sephadex chromatography. Disc electrophoresis and an isoelectric focusing method resolved the neutral enzyme activity into 4 bands. All bands had a similar amino acid analysis and a similar molecular weight by sodium dodecylsulfate electrophoresis and gel filtration: 24,000–27,000 daltons. The enzyme degraded proteoglycan subunit and proteoglycan aggregate to products with a sedimentation coefficient of 3S, but at low dilutions the enzyme produced 19.3S fragments. It is postulated that this protease may contribute to the development of osteoarthritis from within the cartilage matrix.