Fibroblasts represent the major cell type in the dental pulp. They contribute the extracellular matrix which serves to support other cells (macrophages, immune cells, etc.) and structural elements (blood vessels, nerves, etc.) These cells also serve as a source of stem cells for odontoblast replacement when the pulp is injured. It has become apparent that fibroblasts represent a heterogeneous population of cells and can serve as both target and source cells for inflammatory cytokines. Because of their numbers and location, these cells can significantly contribute to the inflammatory response and affect the quantity and quality of matrix produced. We have isolated two distinct types of fibroblasts from human dental pulp. One has an odontoblast-like phenotype (OBL) and has the capacity to form cellular and calcium phosphate nodules in vitro, express alkaline phosphatase activity, and express TGF-beta1 specific mRNA. The other has a typical fibroblast-like phenotype (PF) and exhibits none of these activities. We propose that OBL cells and PF represent two distinct fibroblast populations and that they ma respond to cytokines and transforming growth factors differentially. Furthermore, both PF and OBL cells may play important but distinct roles in the maintaining normal pulpal architecture and defending the pulp against bacterial invasion by their capacity to serve as accessory immune cells. The purpose of this study is to further characterize PF and OBL cells and investigate their role in differentiation and inflammation. The elucidation of the exact characteristics of these cells and the immunological role they play during inflammation will provide an understanding of the basic mechanisms involved in tissue damage and repair that occurs in the pulp. We propose to: (1) Further characterize differences between PF and OBL cells by the assessment of the differential expression of proteins involved in odontoblastic differentiation, such as: TGF-beta1, TGF-beta2, osteocalcin, and dentin phosphoprotein. (2) Establish the role of PF and OBL cells during an immune response, by: (a) assessing the induction of IL-8, IL-6, and IL-1beta mRNA in PF and OBL cells by LPS obtained from Porphyromonas gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa). (b) assessing the induction of IL-8, IL-6, and IL-1beta proteins in PF and OBL cells primed with TNF-alpha or IL-1beta prior to treatment with LPS obtained from the following gram negative periodontal pathogens, Pg and Aa. (3) Elucidate the ability of cytokines produced during an immune response to modulate the functional characteristics of PFs and OBL cells, by: (a) the treatment with proinflammatory cytokines such as, TNF-alpha or IL-1beta, and (b) the treatment with bone morphogenic protein such as TGF-beta1 and TGF-beta2.
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