CTGF in gingival overgrowth

Date
2004
DOI
Authors
Heng, Edwin C.K.
Version
OA Version
Citation
Abstract
Gingival Overgrowth is a well-documented unwanted effect, characterized clinically by excess tissue accumulation. Previous studies showed highly elevated Connective Tissue Growth Factor (CTGF) levels were found in drug-induced overgrowth tissues. Structure/activity relationships for CTGF remain incompletely defined. The objectives of this study are to find (1) the mechanism of how CTGF stimulates collagen accumulation and (2) which domain(s) of CTGF is/are involved in this process. Human gingival fibroblasts derived from explants of normal gingival tissues (N5 culture) were cultured to full confluence in multi-well tissue culture plates. Cells were then treated (2-day regular medium changes) with 50 ug/ml ascorbate with or without 50 - 100 ng/ml of full length rhCTGF (n = 6 wells) in the presence or absence of CTGF domain specific antibodies or non-immune IgG. Dye-binding assays for collagen accumulation and cell proliferation were performed on harvested cells at Day 7. Bound dye was eluted and quantitated by measuring the absorbance at 550 nm and 590 nm respectively. In multiple experiments, 50 - 100 ng/ml CTGF consistently increased collagen accumulation between 1 and 14% and was dose dependent (p[less than]0.05, student t-test). CTGF produced inconsistent effects on cell proliferation. Increased collagen deposition by CTGF was independently confirmed by biochemical measurements. Collagen accumulation was blocked by Domain 3 antiĀ­ CTGF antibody (p[less than]0.05, students t-test, n = 6 wells). In conclusion, the region of CTGF active in stimulating collagen accumulation by gingival fibroblasts is located in Domain 3, on the C-terminal half of CTGF. A potential therapeutic strategy may include interfering with CTGF stimulated collagen deposition, reducing the need for surgical intervention on patients experiencing gingival overgrowth.
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Thesis (M.S.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2004 (Periodontology and Oral Biology).
Includes bibliographical references (leaves 92-98).
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This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.