The effect of PDGF and IL-I on osteoblast differentiation and production of a mineralized bone matrix

Date
1998
DOI
Authors
Hsieh, Sung-Chih
Version
OA Version
Citation
Abstract
Platelet-derived growth factor (PDGF) stimulates chemotaxis and proliferation of osteoblasts, and induces bone formation in vivo. To determine how PDGF might regulate these cells, the effect of PDGF on long-term mineralizing cultures of fetal rat osteoblastic cells was examined. Although PDGF increased cell proliferation in these cultures, continuous treatment with PDGF caused a dose-dependent decrease in mineralized nodule formation. When cells were treated with multiple, brief (one day) exposures to PDGF at the osteoblast differentiation stage, there was a significant 50% increase in mineralized nodule area. Based on modulation of alkaline phosphatase activity it appears that longer-term exposure to PDGF reduces mineralized nodule formation largely by inhibiting differentiated osteoblast function, while short-term exposure enhances proliferation without inhibiting the differentiated phenotype. Thus, the ultimate affect of PDGF on bone formation is likely to reflect two processes; a positive effect through enhancing cell number or a negative effect by inhibiting differentiated function. The inhibitory effect of PDGF on formation of a mineralized matrix is unlikely to be simply a result of enhanced proliferation of "fibroblastic" cells since cultures treated with PDGF for 3 days and then transferred to new plastic dishes exhibited a 70% increase in mineralized nodule area compared to controls. These results would predict that multiple, brief exposures to PDGF would enhance bone formation in vivo, while prolonged exposure to PDGF, which is likely to occur in chronic inflammation, would inhibit differentiated osteoblast function and limit bone regeneration. Furthermore, IL-1 plus PDGF treatment strongly inhibited the mineralized nodule formation by approximately 95%, in comparison with IL-1 (25%) and PDGF (80%) treatment only. IL-1 plus PDGF significantly decreased the alkaline phosphatase activity as well. Since both may be eleveated in lesions of endodontic origin, persistent expression of PDGF and IL-1 may explain why osseous healing does not occur until successful endodontic treatment is performed.
Description
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Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 1998 (Endodontics).
Includes bibliographical references (leaves 65-94).
License
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