This proposal is a resubmission of a previous grant (AM 28420-04) which was reviewed in June, 1986. This proposal deals with the metabolism and effects of vitamin D metabolites on isolated bone cells.
The specific aims have been refocused 1) to elucidate the role of age on the extra renal metabolism of 25-hydroxy-vitamin D (25(OH)D3) by bone cells, 2) to study the effect of exogenous stimulators of proliferation and differentiation on the metabolism of 25(OH)D3, 3) to refine a cell isolation technique to the point of identifying which bone cell phenotype is responsible for the metabolism of 25(OH)D3 and 4) to purify and study the effect of hormones on bone cell phosphotyrosine phosphatase (PTPase). The long term objectives of this work are to determine whether extra renal metabolism of vitamin D metabolites by bone cells is physiologically important. Moreover, this work will also explore the role of calcitropic hormones in regulating cell proliferation by their action on the newly discovered enzyme, PTPase. Since the previous submission of this proposal new information regarding the regulation of a chick bone cell 25(OH)D3-1- hydroxylase has been obtained. This enzyme appears to be regulated in a complex way by vitamin D metabolites and has been shown to have a short half-life (approximately 5 hours).

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR028420-05
Application #
3155651
Study Section
General Medicine B Study Section (GMB)
Project Start
1982-02-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Martinez, D A; Zuscik, M J; Ishibe, M et al. (1995) Identification of functional insulin-like growth factor-II/mannose-6-phosphate receptors in isolated bone cells. J Cell Biochem 59:246-57
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Puzas, J E; Hicks, D G; Reynolds, S D et al. (1994) Regulation of osteoclastic activity in infection. Methods Enzymol 236:47-58
O'Keefe, R J; Crabb, I D; Puzas, J E et al. (1994) Effects of transforming growth factor-beta 1 and fibroblast growth factor on DNA synthesis in growth plate chondrocytes are enhanced by insulin-like growth factor-I. J Orthop Res 12:299-310

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