Altered Trabecular Bone Structure and Delayed Cartilage Degeneration in the Knees of Collagen VI Null Mice

Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role of collagen VI in the morphology and physical properties of bone and cartilage in the knee joint of Col6a1−/− mice by micro-computed tomography (microCT), histology, atomic force microscopy (AFM), and scanning microphotolysis (SCAMP). Col6a1−/− mice showed significant differences in trabecular bone structure, with lower bone volume, connectivity density, trabecular number, and trabecular thickness but higher structure model index and trabecular separation compared to Col6a1+/+ mice. Subchondral bone thickness and mineral content increased significantly with age in Col6a1+/+ mice, but not in Col6a1−/− mice. Col6a1−/− mice had lower cartilage degradation scores, but developed early, severe osteophytes compared to Col6a1+/+mice. In both groups, cartilage roughness increased with age, but neither the frictional coefficient nor compressive modulus of the cartilage changed with age or genotype, as measured by AFM. Cartilage diffusivity, measured via SCAMP, varied minimally with age or genotype. The absence of type VI collagen has profound effects on knee joint structure and morphometry, yet minimal influences on the physical properties of the cartilage. Together with previous studies showing accelerated hip osteoarthritis in Col6a1−/− mice, these findings suggest different roles for collagen VI at different sites in the body, consistent with clinical data

Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis

The reaction patterns of chondrocytes in osteoarthritis can be summarized in five categories: (1) proliferation and cell death (apoptosis); changes in (2) synthetic activity and (3) degradation; (4) phenotypic modulation of the articular chondrocytes; and (5) formation of osteophytes. In osteoarthritis, the primary responses are reinitiation of synthesis of cartilage macromolecules, the initiation of synthesis of types IIA and III procollagens as markers of a more primitive phenotype, and synthesis of active proteolytic enzymes. Reversion to a fibroblast-like phenotype, known as 'dedifferentiation', does not appear to be an important component. Proliferation plays a role in forming characteristic chondrocyte clusters near the surface, while apoptosis probably occurs primarily in the calcified cartilage

Experimental loss of menisci, cartilage and subchondral bone gradually increases anteroposterior knee laxity

Purpose: Anteroposterior knee stability is a relevant factor for the decision-making process of various surgical procedures. In degenerative joints when the implantation of unicompartimental prostheses or corrective osteotomies of the limb are planned, the integrity of the anteroposterior stability with an intact ACL has been regarded as a necessary prerequisite. We hypothesise that joint degeneration, however, may influence the anteroposterior knee laxity. Therefore, we set out to test this hypothesis simulating a progressively ‘degenerated’ joint in an experimental cadaveric setting. Methods: Twelve intact transfemorally resected Thiel-fixated cadaver knee joints were divided into 2 groups for manipulation in the medial or lateral compartment. In each knee, we performed (1) unilateral total meniscectomy; (2) simulation of advanced osteoarthritis, by unilateral total cartilage debridement; (3) simulation of a unilateral tibial impression fracture, by resection of 5 mm of the tibial plateau; (4) transection of the ACL. The KT-1000 arthrometer was used to measure the extent of anteroposterior translation at 30° of knee flexion. Results: The mean value for tibial anteroposterior translation before intervention was 3.2 mm (SD: ±0.8). The mean translation after each intervention was 4.6 mm (SD: ±0.9; +44%; n.s.) after meniscectomy, 5.9 mm (SD: ±1.5; +84%; P < 0.05) after cartilage debridement, 8 mm (SD: ±1.5; +150%; P < 0.01) after bone debridement, and finally 9.7 mm (SD: ±2.2; +203%; P < 0.05) after resection of the ACL. There were no significant differences between the medial and lateral compartment. Conclusion: In absence of massive osteophytes or capsular shrinkage, rapid loss of meniscus, cartilage and particularly loss of subchondral bone may result in a massive increase in anteroposterior translation, mimicking a tear of the ACL. In such a situation, a false positive impression of a ligamentous injury may arise, and decision making is falsely directed away from totally or partially knee joint-preserving procedures. Therefore, in degenerate joints, clinical evaluation of anteroposterior stability should rather rely on the presence of a firm stop than an overall increased joint translation