Bone has considerable potential for repair and regeneration. In adults these events are locally regulated by cytokines. One of the cytokines that potentially plays a significant role in bone regeneration is platelet-derived growth factor. Evidence that PDGF may be an important mediator of bone regeneration stems from findings that it is stored in bone, has the capacity to stimulate bone cells, is produced by bone cells, and is generated in wound healing environments. Despite the above evidence, there have been few studies to investigate the capacity of normal human osteoblastic cells to synthesize and respond to PDGF. It is the goal of this proposal to investigate the potential role of PDGF as a bone regulatory cytokine by studying PDGF synthesis and response in vitro in normal human osteoblastic cells. In order to accomplish this objective we will establish normal human adult osteoblastic cell populations consisting of bone cell explants and cells cloned from these explants. These bone cells will be thoroughly characterized for the osteoblastic phenotype. We will investigate the synthesis of PDGF by these cells and determine which factors regulate expression of the two PDGF genes, PDGF-A and PDGF-B. We will also examine the response of bone-derived cells to each PDGF isoform, PDGF-AB, PDGF-BB, PDGF-AA. This will be studied on several levels; 125I PDGF binding, the induction of secondary messages, the induced expression of specific genes, stimulation of DNA synthesis, cellular proliferation and formation of an in vitro mineralizing matrix. And finally, we will determine if the production of PDGF and response to PDGF leads to autocrine stimulation in normal human osteoblastic cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009581-05
Application #
2130637
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1990-09-30
Project End
1995-09-29
Budget Start
1994-09-30
Budget End
1995-09-29
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Boston University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Yu, X; Hsieh, S C; Bao, W et al. (1997) Temporal expression of PDGF receptors and PDGF regulatory effects on osteoblastic cells in mineralizing cultures. Am J Physiol 272:C1709-16
Young, S J; Chaibi, M S; Graves, D T et al. (1996) Quantitative analysis of periodontal defects in a skull model by subtraction radiography using a digital imaging device. J Periodontol 67:763-9
Kose, K N; Xie, J F; Carnes, D L et al. (1996) Pro-inflammatory cytokines downregulate platelet derived growth factor-alpha receptor gene expression in human osteoblastic cells. J Cell Physiol 166:188-97
Oates, T W; Kose, K N; Xie, J F et al. (1995) Receptor binding of PDGF-AA and PDGF-BB, and the modulation of PDGF receptors by TGF-beta, in human periodontal ligament cells. J Cell Physiol 162:359-66
Kang, Y M; Yeh, Y L; Graves, D T (1995) Interleukin-1 modulates phosphorylation of proteins in human osteoblastic cells. J Bone Miner Res 10:96-105
Rahimi, P; Wang, C Y; Stashenko, P et al. (1995) Monocyte chemoattractant protein-1 expression and monocyte recruitment in osseous inflammation in the mouse. Endocrinology 136:2752-9
Xie, J F; Stroumza, J; Graves, D T (1994) IL-1 down-regulates platelet-derived growth factor-alpha receptor gene expression at the transcriptional level in human osteoblastic cells. J Immunol 153:378-83
Zhu, J F; Valente, A J; Lorenzo, J A et al. (1994) Expression of monocyte chemoattractant protein 1 in human osteoblastic cells stimulated by proinflammatory mediators. J Bone Miner Res 9:1123-30
Jiang, Y; Zhu, J F; Luscinskas, F W et al. (1994) MCP-1-stimulated monocyte attachment to laminin is mediated by beta 2-integrins. Am J Physiol 267:C1112-8
Yeh, Y L; Kang, Y M; Chaibi, M S et al. (1993) IL-1 and transforming growth factor-beta inhibit platelet-derived growth factor-AA binding to osteoblastic cells by reducing platelet-derived growth factor-alpha receptor expression. J Immunol 150:5625-32

Showing the most recent 10 out of 15 publications