Alveolar destruction in the periodontal diseases is strikingly localized. The precise etiological agents responsible for this pattern of disease are not known. Much work has centered on microbiological floras yet little information exists to explain the disease pattern. Host factors are also thought to be important. The specific components and the mechanisms involved in the host response are, however, not clear. Extracellular matrix components have been shown to have profound effects on connective tissue cells. It is the overall objective of this proposal to enhance our concept of the host response in periodontal disease pathogenesis. The specific aim is to examine the role of extracellular matrix molecules in the bone resorption process and to investigate the mechanisms by which bone resorption occurs in the presence of these molecules. In particular, the effect of hyaluronic acid, chondroitin sulfate A and C and dermatan sulfate on in vitro bone resorption in the presence and absence of PTH will be examined and compared to know effects of heparin under similar conditions. In addition, the amount of latent collagenase, active collagenase and PGE2 released in the culture medium will be determined. The results from these experiments will provide a basis for future experiments examining the role of these molecules on the specific cellular components involved in bone resorption. Furthermore, these experiments will investigate, at the molecular level, how proteoglycans affect bone resorption and will therefore enhance our concept of the role of the host response in the localized alveolar destruction observed in the periodontal diseases.