Objective. Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the "pericellular matrix" (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading.Methods. Col6a1 ؊/؊ mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1-monthold Col6a1 ؊/؊ , Col6a1 ؉/؊ , and Col6a1 ؉/؉ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique.
Results. In Col6a1؊/؊ and Col6a1 ؉/؊ mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wildtype controls. With age, Col6a1 ؊/؊ mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD.Conclusion. These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1 ؊/؊ -derived joint laxity, can lead to progression of OA.Articular cartilage is the tissue that lines the surfaces of diarthrodial joints and serves as the resilient, low-friction, load-bearing material for joint motion. A sparse population of cells-chondrocytes-maintains the extracellular matrix (ECM) of this tissue through a balance of anabolic and catabolic activities. The micromechanical environment of chondrocytes, in conjunction with biochemical factors (e.g., growth factors, cytokines) and genetic factors, plays an important role in cartilage homeostasis and, as a consequence, the health of the joint (1-3). Chondrocytes in articular cartilage are enclosed by a narrow region of tissue termed the "pericellular matrix" (PCM), which, together with the enclosed chondrocyte, has been termed the "chondron" (4-7). The PCM is characterized primarily as being the exclusive location of type VI collagen in normal cartilage, but proteoglycans, fibronectin, and types II and IX collagen are also pre...