This research is examines mechanisms by which membranes, particularly matrix vesicles, promote biological mineralization. Various components of the membrane, including ion-transporting proteolipids, phospholipids, alkaline phosphatase and phospholipase A2, are involved in perturbation of the system by vitamin D provides an excellent opportunity to dissect the membrane-dependent mineralization process. The research proposed will use a chondrocyte culture model to address the following Specific Aims. (1) To determine whether chondrocytes produce vitamin D metabolites as paracrine or autocrine regulators of cell and matrix vesicle function. Regulation of 14C-25-(OH)D3 metabolism by exogenous 1,25-(OH)2D3, 24,25-(OH)2D3, TGFb and dexamethasone will be characterized. The presence of radiolabeled metabolite in the plasma isolated membranes will indicate whether secreted metabolites can act as autocrine or paracrine agents. (2) To examine effects of vitamin D metabolites on membrane signaling systems. Effects of Vitamin D metabolites on inositol phosphate turnover, acylation and reacylation of phospholipids, production of endogenous PGE2 ( and membrane response to exogenous PGE2), and membrane fluidity will be studied. (3) To characterize the membrane effects of vitamin D metabolites on functional properties of matrix vesicles. Steroid hormone effects on kinetic properties of purified phosphatidyinositol-linked and phosphatidyl inositol-free alkaline phosphatase activity will be compared to that in native matrix vesicles. These results will be correlated with effects of steroid hormones on matrix vesicle mineralization in culture and in vitro. The chondrocyte culture model affords an opportunity to better understand mechanisms of vitamin D action in chondrogenesis and cartilage cell metabolism. The studies have immediate implications in fracture healing, osteoporosis, vitamin D deficiency diseases and normal bone growth and development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005937-11
Application #
3219670
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1981-03-01
Project End
1996-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Kinney, R C; Schwartz, Z; Week, K et al. (2005) Human articular chondrocytes exhibit sexual dimorphism in their responses to 17beta-estradiol. Osteoarthritis Cartilage 13:330-7
Schwartz, Z; Carney, D H; Crowther, R S et al. (2005) Thrombin peptide (TP508) treatment of rat growth plate cartilage cells promotes proliferation and retention of the chondrocytic phenotype while blocking terminal endochondral differentiation. J Cell Physiol 202:336-43
Schwartz, Z; Graham, E J; Wang, L et al. (2005) Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes. J Cell Physiol 203:54-70
Gay, I; Schwartz, Z; Sylvia, V L et al. (2004) Lysophospholipid regulates release and activation of latent TGF-beta1 from chondrocyte extracellular matrix. Biochim Biophys Acta 1684:18-28
Boyan, B D; Schwartz, Zvi (2004) Rapid vitamin D-dependent PKC signaling shares features with estrogen-dependent PKC signaling in cartilage and bone. Steroids 69:591-7
Boyan, B D; Jennings, E G; Wang, L et al. (2004) Mechanisms regulating differential activation of membrane-mediated signaling by 1alpha,25(OH)2D3 and 24R,25(OH)2D3. J Steroid Biochem Mol Biol 89-90:309-15
Boyan, Barbara D; Dean, David D; Sylvia, Victor L et al. (2003) Steroid hormone action in musculoskeletal cells involves membrane receptor and nuclear receptor mechanisms. Connect Tissue Res 44 Suppl 1:130-5
Schwartz, Z; Shaked, D; Hardin, R R et al. (2003) 1alpha,25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-beta activity via phospholipase A2-dependent production of lysophospholipid. Steroids 68:423-37
Boyan, Barbara D; Sylvia, V L; McKinney, N et al. (2003) Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice. J Cell Biochem 90:1207-23
Lohmann, C H; Schwartz, Z; Liu, Y et al. (2003) Pulsed electromagnetic fields affect phenotype and connexin 43 protein expression in MLO-Y4 osteocyte-like cells and ROS 17/2.8 osteoblast-like cells. J Orthop Res 21:326-34

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