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, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM018063-12
Application #
3151111
Study Section
General Medicine B Study Section (GMB)
Project Start
1975-03-01
Project End
1990-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

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

  Publications

Sakuma, Yoko; Li, Ziaodong; Pilbeam, Carol C et al. (2004) Stimulation of cAMP production and cyclooxygenase-2 by prostaglandin E(2) and selective prostaglandin receptor agonists in murine osteoblastic cells. Bone 34:827-34
Li, Xiaodong; Tomita, Masato; Pilbeam, Carol C et al. (2002) Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo. Prostaglandins Other Lipid Mediat 67:173-80
Li, X; Pilbeam, C C; Pan, L et al. (2002) Effects of prostaglandin E2 on gene expression in primary osteoblastic cells from prostaglandin receptor knockout mice. Bone 30:567-73
Okada, Y; Lorenzo, J A; Freeman, A M et al. (2000) Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture. J Clin Invest 105:823-32
Li, X; Okada, Y; Pilbeam, C C et al. (2000) Knockout of the murine prostaglandin EP2 receptor impairs osteoclastogenesis in vitro. Endocrinology 141:2054-61
Raisz, L G (1999) Physiology and pathophysiology of bone remodeling. Clin Chem 45:1353-8
Kawaguchi, H; Raisz, L G; Voznesensky, O S et al. (1994) Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae. Endocrinology 135:1157-64
Prestwood, K M; Pilbeam, C C; Burleson, J A et al. (1994) The short-term effects of conjugated estrogen on bone turnover in older women. J Clin Endocrinol Metab 79:366-71
Pilbeam, C C; Alander, C B; Simmons, H A et al. (1993) Comparison of the effects of various lengths of synthetic human parathyroid hormone-related peptide (hPTHrP) of malignancy on bone resorption and formation in organ culture. Bone 14:717-20
Marusic, A; Raisz, L G (1991) Cortisol modulates the actions of interleukin-1 alpha on bone formation, resorption, and prostaglandin production in cultured mouse parietal bones. Endocrinology 129:2699-706

Showing the most recent 10 out of 32 publications