REGULATION OF PERIODONTAL CELLS BY CEMENTUM COMPONENTS

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Cementum is the mineralized tissue which covers the roots of the teeth. Connective tissues of the periodontal ligament and gingiva are attached to the teeth through cementum, and this attachment is essential for tooth anchorage and tooth mobility. The cementum is deposited on growing tooth surfaces during tooth eruption and very little is known about the molecules, cells and mechanisms involved in cementogenesis. New cementum formation is necessary t restore connective tissue attachment lost as a result of periodontitis, however, this can be predictably achieved is not known. We and others have shown that the cementum matrix contains adhesion molecules and growth factors which influence the biological activities of periodontal cells. We have isolated and partially characterize one of the adhesion molecules, a 56 kDa attachment protein, and produced monoclonal antibodies against this protein. We demonstrated that this protein, cementum attachment protein (CAP), is present in cementum and not detectable in other periodontal tissues. Amino acid sequence showed that the CAP is an apparently novel collagenous protein. Periodontal ligament cells which bind CAP with high specific binding, not those with low specific binding, form mineralized tissue in culture and produce CAP. Based on these observations we propose that the CAP is a distinct cementum protein which participates in cementogenesis by recruiting cementoblast precursor cells and regulating their activities. We will isolate cDNAs for this protein by screening a cDNA library made from a cementum tumor cell strain which produces CAP, and express this protein in vitro. Using periodontal ligament cells which produce the CAP, we will study its biosynthesis and maturation and how its production is regulated. We will investigate how the CAP interacts with periodontal cells by characterizing its binding to its receptors. We will assess if the CAP affects mineralized tissue formation and regulates the expression of cementum matrix proteins. Finally, we will assess if the biological actions of CAP are influenced by cementum-derived growth factor, a growth factor present in cementum. From these studies we expect to elucidate the molecular structure, biosynthesis and function of the CAP, and understand how this protein participates in cementum formation. We expect these studies to provide insights into the mechanisms of cementogenesis in children and help to design rational therapeutic procedures to form new cementum and connective tissue attachment to previously diseased roots and on endosseous implants.