Regulation of platelet-derived growth factor receptors in human osteoblastic cells and periodontal ligament cells

Date
1997
DOI
Authors
Kose, Kemal Naci
Version
OA Version
Citation
Abstract
Bone has the capacity to repair and regenerate. Platelet derived growth factor (PDGF) is thought to play a significant role in skeletal development, bone repair and regeneration, as well as in periodontal regeneration. Multiple mediators, such as proinflammatory mediators, steroid hormones, growth factors and cytokines have been suggested to play an important role in regulating PDGF mediated events. Interleukin- I (IL-1) and tumor necrosis factor-alpha (TNF-a) are potent bone resorptive cytokines, generated in osseous and periodontal inflammation. Therefore, the inhibitory effects of these cytokines might involve the modulation of the effects of potent connective tissue growth factors including platelet-derived growth factor (PDGF). Studies presented here indicate that TNF-a significantly reduces PDGF-AA binding to normal human osteoblastic cells by decreasing the number of PDGF-a receptor subunits on the cell surf ace. These results are concomitant with a decrease in PDGF-AA stimulated tyrosine kinase activity. When saturating concentrations of TNF-a were used, the addition of IL-I further inhibited the binding of PDGF-AA to osteoblastic cells and further decreased surlace expression of PDGF-a receptors. In contrast, other mediators, IL-6, parathyroid hormone (PTH), 1,25 dihydroxy vitamin D3 (1,25(0Hh vit D3), hydrocortisone, prostaglandin E2 (PGE2), basic fibroblast growth factor (bFGF), and insulin-like growth factor-I (IGF-1) had no effect. These results suggest that the strong proinflammatory cytokines, IL-I and TNF-a, decreased the amount of bound PDGF to normal human osteoblastic cells. This effect is specific for IL-I and TNF-a rather than a general response to mediators of bone resorption or formation. [TRUNCATED]
Description
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please log in with a valid BU account to access and click Download. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.
Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 1997 (Oral Biology).
Includes bibliographical references (leaves 119-167).
License
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.