The proposed research Is directed at enhancing our understanding of the molecular basis for the alteration in collagen types observed in the gingival connective tissues of patients with inflammatory periodontal disease. Of specific interest is the role of the stress protein Hsp47 in the synthesis and distribution of a new collagen, type I homotrimer, which is detected at sites of gingival inflammation. The hypothesis that will be tested in the following proposal is that the collagen produced by fibroblasts derived from inflamed, or diseased, gingiva, which is enriched with type I homotrimers, reflects a subpopulation of fibroblasts that (1) fail to express transcripts for the alpha2(l) collagen gene and/or (2) lack sufficient quantities of the collagen binding glycoprotein, Hsp47, that plays a key role in chaperoning the assembly of type I collagen heteropolymers.
The specific aims of the project will clarify our understanding of the biologic basis for the alteration in collagen of inflamed gingiva by: (1) determining by in situ hybridization the relative expression of transcripts for alpha1(l) and alpha2(l) collagen genes among healthy and inflamed gingiva, (2) establishing by in situ hybridization the relative expression of transcripts for the stress protein Hsp47 among healthy and inflamed gingiva, (3) determining the relative proportion of Hsp47 in gingival fibroblasts derived from healthy and inflamed tissues, and (4) proving that Hsp47 determines the extent of type I collagen homotrimer formation in healthy, or non- inflamed, gingiva by employing nuclease-resistent antisense oligonucleotides for Hsp47, thereby diminishing the cellular levels of Hsp47 and enabling the assembly of type l homotrimer. The studies proposed here will further define the nature of collagenous alterations accompanying inflammatory periodontal disease as well as provide a molecular basis for determining new treatment modalities for wound healing and tissue regeneration.
| Reynolds, Mark A; Aberdeen, Graham W; Pepe, Gerald J et al. (2004) Estrogen suppression induces papillary gingival overgrowth in pregnant baboons. J Periodontol 75:693-701 |
| Reynolds, M A; Bowers, G M (1996) Fate of demineralized freeze-dried bone allografts in human intrabony defects. J Periodontol 67:150-7 |
