Abstract

Regeneration of the periodontal tissues lost due to periodontal disease is one of ultimate goals of periodontal therapy. Current evidence indicates that the progenitor cells for the formation of new connective tissue attachment (new cementum with inserting fibers) on denuded roots are located in the underlying healthy part of the periodontal ligament. The attachment of cells to substrata, their migration, deposition and organization of extracellular matrix are not completely understood. The proposed studies are aimed at elaborating the biologic bases for tissue regeneration in periodontal therapy. Using an in vitro model for the periodontal ligament (PDL) developed in our laboratory, we will analyze the attachment of cells to dental substrata (root dentin, bone) and the organization of extracellular matrix by the cells. Specifically, we will be analyzing the roles of extracellular matrix components (fibronectin, collagen and osteonectin) on cell attachment, migration and differentiation. Reconstituted matrices in simulated periodontal spaces in vitro will be used. By combining in vitro and in vivo techniques, we will determine the ability of gingival, periodontal ligament and alveolar bone-derived cells to form new cementum with inserting fibers on dentin surfaces. Human gingival, PDL and alveolar bone-derived cells will be cultured, characterized, labelled, attached to dentin particles and implanted in nude mice. Finally, regeneration of the periodontal ligament requires the directed migration of progenitor cells. Using chemotactic assays, we will compare the migration rates of cells obtained from gingival, PDL and bone granulation tissue. Also, the attachment of these cells to collagen coated substrata and their cytoskeletal organization during directed migration will be analyzed. Information obtained from the proposed experiments will help us develop a new therapeutic procedure for the predictable regeneration of periodontal ligament. such information is also essential for a better understanding of the physiology of periodontal tissues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007801-03
Application #
3221570
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1988-07-01
Project End
1992-04-30
Budget Start
1990-07-01
Budget End
1992-04-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Dentistry
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Sahlberg, C; Aukhil, I; Thesleff, I (2001) Tenascin-C in developing mouse teeth: expression of splice variants and stimulation by TGFbeta and FGF. Eur J Oral Sci 109:114-24
Aukhil, I (2000) Biology of wound healing. Periodontol 2000 22:44-50
Hashimoto-Uoshima, M; Yan, Y Z; Schneider, G et al. (1997) The alternatively spliced domains EIIIB and EIIIA of human fibronectin affect cell adhesion and spreading. J Cell Sci 110 ( Pt 18):2271-80
Leahy, D J; Aukhil, I; Erickson, H P (1996) 2.0 A crystal structure of a four-domain segment of human fibronectin encompassing the RGD loop and synergy region. Cell 84:155-64
Aukhil, I; Sahlberg, C; Thesleff, I (1996) Basal layer of epithelium expresses tenascin mRNA during healing of incisional skin wounds. J Periodontal Res 31:105-12
Leahy, D J; Erickson, H P; Aukhil, I et al. (1994) Crystallization of a fragment of human fibronectin: introduction of methionine by site-directed mutagenesis to allow phasing via selenomethionine. Proteins 19:48-54
Aukhil, I; Joshi, P; Yan, Y et al. (1993) Cell- and heparin-binding domains of the hexabrachion arm identified by tenascin expression proteins. J Biol Chem 268:2542-53
Joshi, P; Chung, C Y; Aukhil, I et al. (1993) Endothelial cells adhere to the RGD domain and the fibrinogen-like terminal knob of tenascin. J Cell Sci 106 ( Pt 1):389-400
Leahy, D J; Hendrickson, W A; Aukhil, I et al. (1992) Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. Science 258:987-91
Aukhil, I (1991) Biology of tooth-cell adhesion. Dent Clin North Am 35:459-67

Showing the most recent 10 out of 11 publications