Abstract

These studies are designed to determine the pathogenesis of the degenerative arthropathies associated with the deposition of calcium pyrophosphate dihydrate or basic calcium phosphate crystals in articular tissues with the eventual goal of developing a rational means of preventing or reversing the consequences of such deposition. This proposal focuses chiefly on the interaction of living cells with crystals containing calcium. We shall examine how the observed biological effects such as stimulation of mitogenesis, crystal dissolution, arachidonic acid metabolism and proteases synthesis are related to each other. We shall further define the mechanism of BCP crystal-induced mitogenesis with special emphasis on early biochemical changes in cells stimulated by crystals. The mechanism of BCP crystal dissolution by cells will be explored. We are interested in possible intracellular sequestration of Ca2+ resulting from crystal dissolution and rate of Ca2+ efflux. Other related studies will include: level of somatomedin C in joint fluids of arthritis patients; 2) clearance of BCP crystals from human joints. Rabbits and mice will be used as a source for cells for cell culture.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR038421-02
Application #
3158552
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226

  Publications

Huang, C-Y C; Deitzer, M A; Cheung, H S (2007) Effects of fibrinolytic inhibitors on chondrogenesis of bone-marrow derived mesenchymal stem cells in fibrin gels. Biomech Model Mechanobiol 6:5-11
Huang, C-Y Charles; Reuben, Paul M; Cheung, Herman S (2005) Temporal expression patterns and corresponding protein inductions of early responsive genes in rabbit bone marrow-derived mesenchymal stem cells under cyclic compressive loading. Stem Cells 23:1113-21
Cheung, Herman S (2005) Role of calcium-containing crystals in osteoarthritis. Front Biosci 10:1336-40
Sun, Yubo; Reuben, Paul; Wenger, Leonor et al. (2005) Inhibition of calcium phosphate-DNA coprecipitates induced cell death by phosphocitrates. Front Biosci 10:803-8
Reuben, Paul M; Sun, Yubo; Cheung, Herman S (2004) Basic calcium phosphate crystals activate p44/42 MAPK signal transduction pathway via protein kinase Cmicro in human fibroblasts. J Biol Chem 279:35719-25
Sun, Yubo; Firestein, Gary S; Wenger, Leonor et al. (2004) Telomerase-transduced osteoarthritic fibroblast-like synoviocyte cell line. Biochem Biophys Res Commun 323:1287-92
Sun, Yubo; Zeng, Xiao-Rong; Wenger, Leonor et al. (2004) P53 down-regulates matrix metalloproteinase-1 by targeting the communications between AP-1 and the basal transcription complex. J Cell Biochem 92:258-69
Huang, C-Y Charles; Hagar, Kristen L; Frost, Lauren E et al. (2004) Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 22:313-23
Huang, C-Y Charles; Reuben, Paul M; D'Ippolito, Gianluca et al. (2004) Chondrogenesis of human bone marrow-derived mesenchymal stem cells in agarose culture. Anat Rec A Discov Mol Cell Evol Biol 278:428-36
Sun, Yubo; Zeng, Xiao-Rong; Wenger, Leonor et al. (2003) Basic calcium phosphate crystals stimulate the endocytotic activity of cells--inhibition by anti-calcification agents. Biochem Biophys Res Commun 312:1053-9

Showing the most recent 10 out of 52 publications