The major cause of tooth loss after the age of 35 is periodontal disease. The goal of periodontal therapy is stated as providing a dentition that will function in health and comfort for the life of the patient. This goal of providing a functional dentition has led to the development of varied approaches to therapy to preserve the periodontium. Recent reports indicate that this is an achievable goal and that the dentition can be maintained in a healthy functional state. Regeneration of the periodontium is defined as reproduction of reconstitution of a lost or injured part. The biochemical and molecular biological events necessary for regeneration to occur have not been defined. During the last two years we have actively studied biochemical manipulation of dentin surfaces with matrix factors and polypeptide growth factors to try and establish the appropriate conditions to induce periodontal regeneration. These studies indicate that periodontal ligament cells primarily respond chemotactically to TGFBeta and bFGF whereas PDGF is a major mitogenic stimulus. This response is not uniform. Depending on the age of donor we observed low to high responders with """"""""young"""""""" donors responding substantially better than """"""""old"""""""" donors. We observed a decrease in biological response of primary cultures of PDL cells as they are detached and reattached for passage in culture. Further evidence indicates that unattached cells express different molecular biological markers when compared to attached cells. We have observed decreases in specific mRNAs for fibronectin, actin, c- myc, bFgf and PDGF. Addition of PDL-CTX induces a PDL cell phenotype which is consistent with an increased chemotactic and mitogenic response characteristic of young donors. Here we propose to continue to characterize the factors necessary to induce PDL cells to assume a young migratory and mitogenic phenotype. Additionally, we will examine the interaction of various peptides with PDL cells that result in increased or decreased expression of mRNAs for factors necessary for cell survival and proliferation. The interaction of PDL-CTX and bFGF, PDGF and TGFBeta will be examined in relationship to the expression of FN, actin, c-myc, c-sis and c-fos. We will next establish the phenotype characteristic of the """"""""young"""""""" PDL cells. This will be compared and contrasted to aging cultures of PDL cells or """"""""old"""""""" primary cultures of PDL cells. Receptor number and affinity for various polypeptides in addition to expression of mRNAs will be determinants. We will also investigate the cell-cell relationship between endothelial cells (which synthesize and secrete bFGF) and PDL cells. From our studies we hypothesize that as PDL cells age in vitro or in vivo they become less responsive to specific matrix and polypeptide growth factors. We further hypothesize that """"""""old"""""""" PDL cells do not synthesize and secrete adequate concentrations of PDL-CTX to maintain a non senescent phenotype. Finally, as both endothelial cells and PDL cells become more refractive to growth factor stimulation (decrease in angiogenesis and healing potential) the formerly health periodontium becomes susceptible to disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE008188-04A1
Application #
3221979
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1989-09-01
Project End
1994-09-29
Budget Start
1991-09-30
Budget End
1992-09-29
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Dentistry
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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Ye, J; Nishimura, F; Orman, R et al. (1995) Isolation, purification, and partial characterization of an autocrine periodontal ligament cell chemotactic factor. J Dent Res 74:1303-9
Boyan, L A; Bhargava, G; Nishimura, F et al. (1994) Mitogenic and chemotactic responses of human periodontal ligament cells to the different isoforms of platelet-derived growth factor. J Dent Res 73:1593-600
Terranova, V P (1993) Biologically active factors in the treatment of periodontal disease. Curr Opin Periodontol :129-35
Terranova, V P; Price, R M; Morishita, M (1991) Periodontal regeneration: myth or reality? Int Dent J 41:287-94
Lein, P J; Higgins, D; Turner, D C et al. (1991) The NC1 domain of type IV collagen promotes axonal growth in sympathetic neurons through interaction with the alpha 1 beta 1 integrin. J Cell Biol 113:417-28
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Terranova, V P; Odziemiec, C; Tweden, K S et al. (1989) Repopulation of dentin surfaces by periodontal ligament cells and endothelial cells. Effect of basic fibroblast growth factor. J Periodontol 60:293-301