Elucidating the cellular and molecular processes involved in growth and remodeling of skeletal
elements is important for our understanding of
congenital limb deformities. These processes can be advantageously studied in the epiphyseal growth zone, the region in which all of the increase in length of a developing long bone is achieved. Here, young chondrocytes divide, mature, become hypertrophic, and ultimately are removed. During cartilage
hypertrophy, a number of changes occur, including the acquisition of synthesis of new components, the most studied being
type X collagen. In this review, which is based largely on our own work, we will first examine the structure and properties of the
type X collagen molecule. We then will describe the supramolecular forms into which the molecule becomes assembled within tissues, and how this changes its physical properties, such as thermal stability. Certain of these studies involve a novel, immunohistochemical approach that utilizes an antitype X
collagen monoclonal antibody that detects the native conformation of the molecule. We describe the developmental acquisition of the molecule, and its transcriptional regulation as deduced by in vivo footprinting, transient transfection, and gel-shift assays. We provide evidence that the molecule has unique diffusion and regulatory properties that combine to alter the hypertrophic cartilage matrix. These conclusions are derived from an in vitro system in which exogenously added
type X collagen moves rapidly through the cartilage matrix and subsequently produces certain changes mimicking ones that have been shown normally to occur in vivo. These include altering the
cartilage collagen fibrils and effecting changes in
proteoglycans. Last, we describe the subtractive hybridization, isolation, and characterization of other genes up-regulated during cartilage
hypertrophy, with specific emphasis on one of these--
transglutaminase.