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).

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
General Medicine B Study Section (GMB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
School of Medicine & Dentistry
United States
Zip Code
Zuscik, Michael J; O'Keefe, Regis J; Gunter, Thomas E et al. (2002) Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A. J Orthop Res 20:1079-90
Romano, P R; Caton, J G; Puzas, J E (1997) The reversal line may be a key modulator of osteoblast function: observations from an alveolar bone wound-healing model. J Periodontal Res 32:143-7
Rosier, R N; O'Keefe, R J; Teot, L A et al. (1997) P-glycoprotein expression in cartilaginous tumors. J Surg Oncol 65:95-105
Landesberg, R; Takeuchi, E; Puzas, J E (1996) Cellular, biochemical and molecular characterization of the bovine temporomandibular joint disc. Arch Oral Biol 41:761-7
Hicks, D G; Judkins, A R; Sickel, J Z et al. (1996) Granular histiocytosis of pelvic lymph nodes following total hip arthroplasty. The presence of wear debris, cytokine production, and immunologically activated macrophages. J Bone Joint Surg Am 78:482-96
Hughes, S S; Hicks, D G; O'Keefe, R J et al. (1995) Shared phenotypic expression of osteoblasts and chondrocytes in fracture callus. J Bone Miner Res 10:533-44
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
Landesberg, R; Proctor, R L; Rosier, R N et al. (1995) The mandibular condylar growth center: separation and characterization of the cellular elements. Calcif Tissue Int 56:71-7
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

Showing the most recent 10 out of 23 publications