The long term objective of this program is to elucidate the intrinsic regulatory, mechanisms that control the structure and function of the articular cartilage that normally protects and cushions underlying bones. We recently showed that TGF-beta has the ability to prevent the spontaneous proteoglycan loss that occurs in basal, cartilage organ cultures. Our present efforts are directed at 1) gaining a precise understanding of the effects of exogenous TGF-beta administration on the cartilage matrix structure and 2) understanding the endogenous physiology of the TGF-beta isoforms in articular cartilage in order to determine their role in the control of metabolic homeostasis of the tissue.