Abstract

The long term objective of this study is to understand the nature of bone cell calcium regulation. The endogenous and exogenous factors that control this parameter will be assessed and the potential interrelationships between these factors and calcium in the regulation of bone metabolism will be evaluated. The effects of parathyroid hormone (PTH), prostaglandin E2 (PGE2), epidermal growth factor (EGF) and interleukin -I(IL-l) will be studied in normal rat osteoblastic cells and the osteosarcoma lines - UMR-106 and SaOS-2. The interrelationships between putative effects of these agents on calcium and phosphoinositide metabolism will also be studied by investigating the regulation of this phospholipid in the bone cells and by studying the effects of inositol phosphates on calcium mobilization in these isolated cell systems. Interrelationships between arachidonic and cytosolic calcium will also be evaluated and the effects of arachidonic acid on intracellular calcium mobilization will also be studied. The role of protein kinase C in the regulation of osteoblastic calcium metabolism will also be studied using inhibitors and activators of this enzyme. Studies on protein, DNA synthesis and plasminogen activator will also be conducted in an attempt to make correlations with changes in cytosolic calcium. Arachidonic acid metabolism will also be studied in the various cell systems to better understand the interrelationship between cyclooxygenase products and cytosolic calcium. Cytosolic calcium levels will be measured using the Fura 2 fluorescent assay with cells in suspension and attached to coverslips. Phosphoinositol metabolism will be studied with thin layer and ion exchange chromatography and high performance liquid chromatography. Arachidonic acid metabolism will also be studied by high performance liquid chromatography. These studies should lead to a better understanding of the nature of bone cell metabolism and aid in the development of therapy for systemic and localized bone metabolic disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR025271-12
Application #
3155293
Study Section
General Medicine B Study Section (GMB)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
State University of New York at Buffalo
Department
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260

  Publications

Zhang, W; Dziak, R (1996) Tumor necrosis factor alpha stimulates arachidonic acid metabolism in human osteoblastic osteosarcomal cells. Prostaglandins Leukot Essent Fatty Acids 54:427-31
Zhang, W; Dziak, R M; Aletta, J M (1995) EGF-mediated phosphorylation of extracellular signal-regulated kinases in osteoblastic cells. J Cell Physiol 162:348-58
Dziak, R (1993) Biochemical and molecular mediators of bone metabolism. J Periodontol 64:407-15
Zhang, W; Dziak, R (1993) Effects of interleukin-1 alpha on arachidonic acid metabolism in human osteosarcoma osteoblastic cells. Prostaglandins Leukot Essent Fatty Acids 49:521-6
Ren, W; Kinniburgh, A J; Dziak, R (1992) Regulation of C-myc protooncogene expression in osteoblastic cells by arachidonic acid metabolites: relationship to proliferation. Calcif Tissue Int 50:372-7
Kohl, A C; Tatakis, D N; Hansen, C et al. (1992) Effects of interleukin-1, tumor necrosis factor -beta, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells. Calcif Tissue Int 50:129-33
Tatakis, D N; Schneeberger, G; Dziak, R (1991) Recombinant interleukin-1 (IL-1) stimulates prostaglandin E2 production by osteoblastic cells: role of calcium, calmodulin, and cAMP. Lymphokine Cytokine Res 10:95-9
Ren, W; Dziak, R (1991) Effects of leukotrienes on osteoblastic cell proliferation. Calcif Tissue Int 49:197-201
Falsafi, R; Tatakis, D N; Hagel-Bradway, S et al. (1991) Effects of inositol trisphosphate on calcium mobilization in bone cells. Calcif Tissue Int 49:333-9
Shapiro, S; Tatakis, D N; Dziak, R (1990) Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP. Calcif Tissue Int 46:60-2

Showing the most recent 10 out of 12 publications