TYPE X COLLAGEN IN THE AGING SKELETON

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Type X collagen is a short chain collagen which is synthesized almost exclusively by the most mature chondrocytes in cartilage near the calcification front at the cartilage-bone junction. It is a specific biosynthetic marker for the terminal stage of chondrocyte differentiation during endochondral bone formation. This molecule is not synthesized by other cells nor do immature chondrocytes make it until they have enlarged, that is reached a hypertrophic stage. In the growth plate this is the final stage of the chondrocyte life cycle when these cells initiate the mineralization process and then die by apoptosis. The majority of the information on the association of type X collagen with cartilage cell differentiation comes from embryonic studies on nonhuman cartilage. Little is known about the appearance of type X collagen in the aging human skeleton. Several laboratories have reported the appearance of type X collagen in osteoarthritic cartilage, in matrix vesicles of osteoarthritic cartilage, in the formation of bony spurs (osteophytes) and with the movement of the mineralization front (tidemark). The goal of these studies will be to evaluate the prevalence of type X collagen during the normal aging of adult human cartilage. A second goal is to evaluate the potential of human articular chondrocytes isolated from tissue donors of different ages to synthesize type X collagen in response to elevated concentrations of calcium ions and nitric oxide. An understanding of the chondrocyte differentiation process in the aging skeleton will provide a foundation for therapeutic intervention in disorders like OA which are most prevalent in the elderly.