Abstract

The regulation of bone resorption and formation by systemic hormones and local factors will be studied using animal models and organ and cell cultures. The effects of local factors including prostaglandins, macromolecular stimulators and inhibitors of bone resorption will be examined. The products of arachidonic acid metabolism in bone will be characterized and the effects of eiconsanoids on bone formation analyzed. The relation of local stimulators and inhibitors to osteoclast activating factor and other stimulators of bone resorption will be examined both chemically and biologically. Studies on systemic hormones will include analysis of the anabolic effect of PTH, the paradoxical osteomalacia produced by toxic doses of 1,25-(OH)2D and studies on the mechanism of escape from calcitonin. Glucocorticoids will be analyzed for their dual effects and for their relation to changes in endogenous prostaglandin production. New models will be developed for the study of hormonal regulation of mineralization and for the analysis of the role of sex hormones in bone metabolism. These studies are intended to increase our understanding of physiologic and pathologic regulation of bone metabolism and to provide new insight in the pathogenesis of metabolic bone disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR018063-13
Application #
3154967
Study Section
General Medicine B Study Section (GMB)
Project Start
1975-03-01
Project End
1990-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga et al. (2010) Basal bone phenotype and increased anabolic responses to intermittent parathyroid hormone in healthy male COX-2 knockout mice. Bone 47:341-52
Blackwell, Katherine A; Raisz, Lawrence G; Pilbeam, Carol C (2010) Prostaglandins in bone: bad cop, good cop? Trends Endocrinol Metab 21:294-301
Gao, Qi; Xu, Manshan; Alander, Cynthia B et al. (2009) Effects of prostaglandin E2 on bone in mice in vivo. Prostaglandins Other Lipid Mediat 89:20-5
Blackwell, Katherine A; Hortschansky, Peter; Sanovic, Srdan et al. (2009) Bone morphogenetic protein 2 enhances PGE(2)-stimulated osteoclast formation in murine bone marrow cultures. Prostaglandins Other Lipid Mediat 90:76-80
Gao, Qi; Zhan, Peili; Alander, Cynthia B et al. (2009) Effects of global or targeted deletion of the EP4 receptor on the response of osteoblasts to prostaglandin in vitro and on bone histomorphometry in aged mice. Bone 45:98-103
Choudhary, Shilpa; Alander, Cynthia; Zhan, Peili et al. (2008) Effect of deletion of the prostaglandin EP2 receptor on the anabolic response to prostaglandin E2 and a selective EP2 receptor agonist. Prostaglandins Other Lipid Mediat 86:35-40
Kaneko, H; Mehrotra, M; Alander, C et al. (2007) Effects of prostaglandin E2 and lipopolysaccharide on osteoclastogenesis in RAW 264.7 cells. Prostaglandins Leukot Essent Fatty Acids 77:181-6
Choudhary, Shilpa; Halbout, Philippe; Alander, Cynthia et al. (2007) Strontium ranelate promotes osteoblastic differentiation and mineralization of murine bone marrow stromal cells: involvement of prostaglandins. J Bone Miner Res 22:1002-10
Alander, Cynthia B; Raisz, Lawrence G (2006) Effects of selective prostaglandins E2 receptor agonists on cultured calvarial murine osteoblastic cells. Prostaglandins Other Lipid Mediat 81:178-83
Xu, Manshan; Choudhary, Shilpa; Goltzman, David et al. (2005) Do cyclooxygenase-2 knockout mice have primary hyperparathyroidism? Endocrinology 146:1843-53

Showing the most recent 10 out of 49 publications