The removal of mineralized bone matrix as a component of skeletal modeling, remodeling and fracture healing is the responsibility of large, multinucleated giant cells termed osteoclasts. Because osteiclasts occur in low abundance in bone and cannot be grown in tissue culture, they are poor candidates for many conventional experimental techniques. Consequently, despite their indoubted importance in overall skeletal function and calcium homeostasis, relatively little is known about their essentials physiology and chemistry. To help rectify these deficiencies and to provide a new approach to exploring diseases involving osteoclast dysfuncstion (e.g. osteopetrisis, Paget's Disease), we propose to do the following: (1) DEVELOP OSTEOCLAST SPECIFIC cDNA LIBRARIES using cDNA-mRNA hybrid selection techniques and nucleotides derived from authetic osteoclases, peripheral blood monocytes (less mature, mononuclear cells belonging to the same cell family) and foreign body giant cells (multinucleated cells phenotypically similar to osteiclasts); (2) employ selected cDNA probes to (a) CHARACTERIZE THOSE mRNAs specific FOR OR CLOSELY ASSOCIATED WITH OSTEOCLASTS AND (b) ASSESS CHANGES IN OSTEOCLAST SPECIFIC/ASSSOCIATED mRNAs IN RESPONSE TO RESORPTION REGULATING EXOGENOUS AGENTS (e.g., calcitonin, vitamin D3); (3) IDENTIFY AND CHARACTERIZE cDNA CLONES CORRESPONDING TO EXTANT OSTEOCLAST and/or GIANT SPECIFIC MONOCLONAL ANTIBODIES.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR037716-01
Application #
3158298
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1986-02-01
Project End
1989-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Gazit, D; Zilberman, Y; Turgeman, G et al. (1999) Recombinant TGF-beta1 stimulates bone marrow osteoprogenitor cell activity and bone matrix synthesis in osteopenic, old male mice. J Cell Biochem 73:379-89
Gazit, D; Zilberman, Y; Ebner, R et al. (1998) Bone loss (osteopenia) in old male mice results from diminished activity and availability of TGF-beta. J Cell Biochem 70:478-88
Shi, S; Kirk, M; Kahn, A J (1996) The role of type I collagen in the regulation of the osteoblast phenotype. J Bone Miner Res 11:1139-45
Kirk, M D; Kahn, A J (1995) Extracellular matrix synthesized by clonal osteogenic cells is osteoinductive in vivo and in vitro: role of transforming growth factor-beta 1 in osteoblast cell-matrix interaction. J Bone Miner Res 10:1203-8
Scott, D K; Weaver, W R; Clohisy, J C et al. (1992) Regulation of an H-ras-related transcript by parathyroid hormone in rat osteosarcoma cells. Mol Endocrinol 6:1425-32
Hilliard, T J; Meadows, G; Kahn, A J (1990) Lysozyme synthesis in osteoclasts. J Bone Miner Res 5:1217-22
Perry 3rd, H M; Skogen, W; Chappel, J et al. (1989) Partial characterization of a parathyroid hormone-stimulated resorption factor(s) from osteoblast-like cells. Endocrinology 125:2075-82