There is a general agreement that during development the extracellular environment plays a critical role in controlling cell differentiation. However the exact factors responsible for promoting cell differentiation remain to be elucidated. Data generated from numerous studies support the possibility that candidates for this role (including differentiation of cells during cementogenesis), are cell attachment proteins and their corresponding cell receptors. The hypothesis upon which this proposal is based is that cell attachment proteins and their corresponding receptors are expressed in a unique fashion during cementogenesis. We predict that a precisely timed expression of these proteins in critical to the process of cementum formation. Specifically, the studies detailed in this proposal are directed at cementum formation. They will identify and characterize attachment proteins associated with cementum and their corresponding receptors and determine their expression during cementogenesis. While significant advances have been made in understanding dentinogenesis and amelogenesis, limited information has been obtained on the factors regulating cementogenesis. The major objectives of these studies are to 1) identify and characterize cell attachment proteins associated with the extracellular matrix of cementum; 2) determine in developing systems (in vivo and in vitro), the spacial and temporal localization of these proteins, pre and post cementogenesis, using immunological and nucleic acid probes; and 3) identify and characterize receptors for these proteins from periodontal derived fibroblasts and determine their expression during molar root formation. These studies will provide information on the role of attachment proteins and their corresponding receptors during cementogenesis. The information obtained from these studies may permit new and improved clinical periodontal treatments that could greatly diminish the effects of periodontal disease. For example, proteins may be identified that when applied to root surfaces will induce cell differentiation and/or cell attachment and subsequently periodontal regeneration. Moreover, this research will generate new knowledge on the factors regulating tissue development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009532-04
Application #
3223289
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1991-01-01
Project End
1994-03-31
Budget Start
1992-07-01
Budget End
1994-03-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Dentistry
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhang, Hai; Tompkins, Kevin; Garrigues, Jacques et al. (2010) Full length amelogenin binds to cell surface LAMP-1 on tooth root/periodontium associated cells. Arch Oral Biol 55:417-25
Fong, H; Foster, B L; Sarikaya, M et al. (2009) Structure and mechanical properties of Ank/Ank mutant mouse dental tissues--an animal model for studying periodontal regeneration. Arch Oral Biol 54:570-6
Nagatomo, Kanako J; Tompkins, Kevin A; Fong, Hanson et al. (2008) Transgenic overexpression of gremlin results in developmental defects in enamel and dentin in mice. Connect Tissue Res 49:391-400
Hakki, Sema S; Wang, Dian; Franceschi, Renny T et al. (2006) Bone sialoprotein gene transfer to periodontal ligament cells may not be sufficient to promote mineralization in vitro or in vivo. J Periodontol 77:167-73
Swanson, Erica C; Fong, Hanson K; Foster, Brian L et al. (2006) Amelogenins regulate expression of genes associated with cementoblasts in vitro. Eur J Oral Sci 114 Suppl 1:239-43; discussion 254-6, 381-2
Nemoto, E; Darveau, R P; Foster, B L et al. (2006) Regulation of cementoblast function by P. gingivalis lipopolysaccharide via TLR2. J Dent Res 85:733-8
Hakki, Sema S; Nohutcu, Rahime M; Hakki, Erdogan E et al. (2005) Dexamethasone and basic-fibroblast growth factor regulate markers of mineralization in cementoblasts in vitro. J Periodontol 76:1550-8
Chun, Yong-Hee P; Foster, Brian L; Lukasavage, Patricia A et al. (2005) Bisphosphonate modulates cementoblast behavior in vitro. J Periodontol 76:1890-900
Fong, Hanson K; Foster, Brian L; Popowics, Tracy E et al. (2005) The crowning achievement: getting to the root of the problem. J Dent Educ 69:555-70
Foster, B L; Somerman, M J (2005) Regenerating the periodontium: is there a magic formula? Orthod Craniofac Res 8:285-91

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