Hypertrophic repair of articular cartilage in experimental osteoarthrosis.

Abstract

SUMMARY Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodelling of articular cartilage in response to abnormal mechanical stresses is postulated.Experimental osteoarthritis offers a unique opportunity for the study of the initial events leading to cartilage destruction, which is the main characteristic of the disease. Various models of osteoarthritis can be used,' but joint laxity induced by section of a cruciate ligament of the knee or meniscectomy is now considered the most valid method.2-6 Joint-laxityinduced osteoarthritis has been used for numerous biochemical and metabolic studies, and changes in water content and proteoglycan preceding the appearance of cartilage fibrillation have been demonstrated.4 5 In contrast the early histological changes are far less documented, and histomorphometric data are still lacking.Here we report the results of a study of the qualitative and quantitative histological changes preceding cartilage fibrillation induced by section of the anterior cruciate ligament of the dog's knee. We restricted the study to the cartilage of the patella and femoral condyle, which is only slowly affected by fibrillation. Histological data were correlated with glycosaminoglycan and water content. were used. They were of unselected breed and of both sexes, were 3 to 8 years old, and weighed 16 to 30 kg. Absence of prior osteoarthritis was established by clinical examination and during surgical procedures. The dogs were anaesthetised with intravenous sodium pentothal. The anterior cruciate ligament in the right knee of each dog was exposed through a median parapatellar incision and transected with a scalpel, care being taken to avoid damage to the articular surfaces. The left knee was used as control. No sham operations were performed, since no cartilage changes have been shown to be induced by this procedure.5 Postoperatively all animals were kept in pens large enough to allow walking and running. They were killed at regular intervals with an overdose of sodium pentothal, the duration of survival varying from 0 5 to 8 months after surgery.Preparation ofsections. Immediately after killing, both knees were op...

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

“…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.…”

“…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.…”

“…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).…”

Spontaneous and experimental osteoarthritis in dog: Similarities and differences in proteoglycan levels

“…In the ACL-OA dogs, however, aggrecan content did not decrease as in the spontaneous-OA samples, rather a 26% increase was measured when compared to the control cartilage. The increase of aggrecan content may be the consequence of hypertrophic cartilage repair [3,37], which was observed in ACL-dogs 4-48 weeks after surgery [22,24,25]. It is surprising, however, that chondrocytes are still at this stage 2 years after surgery, when the extent of cartilage damage indicate a more advanced stage of the disease.…”

Distinct Transglutaminase 2-independent and Transglutaminase 2-dependent Pathways Mediate Articular Chondrocyte Hypertrophy

“…But in OA, foci of articular chondrocyte hypertrophy develop, typically near sites of cartilage surface lesions (8,9). Chondrocyte hypertrophy in OA may function partly to modulate matrix remodeling and repair (10) and partly to promote calcification, as hypertrophic chondrocytes are commonly co-localized with deposits of hydroxyapatite and calcium pyrophosphate dihydrate crystals in the disease (11). Significantly, deposits of hydroxyapatite and calcium pyrophosphate dihydrate crystals crystals can stimulate intra-articular inflammation and further damage to cartilage in OA (12,13).…”