We have identified a novel factor which stimulates the formation of osteoclasts and which is produced by a human tumor as well as by leukocytes which have been stimulated with concanavalin A. We have called this peptide osteoclastpoietic factor (OPF). We have obtained amino acid sequence on this peptide and found that it is novel and distinct from other known growth regulatory factors, interleukins, and colony stimulating factors. We have found that a synthetic peptide which corresponds to this amino acid sequence mimics the biological effects, and we have produced both monoclonal and polyclonal antibodies which neutralize the original biological activity. In this project, we plan to: 1. Clone the gene and express the recombinant molecule. 2. Determine the role of OPF in normal bone remodeling and in disease states associated with increased bone resorption. Characterization of novel cytokines which are powerful stimulators of osteoclastic bone resorption is likely to lead to new insights in the normal control of osteoclast function and in the pathophysiology of disease states associated with bone destruction.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Xu, S C; Harris, M A; Rubenstein, J L et al. (2001) Bone morphogenetic protein-2 (BMP-2) signaling to the Col2alpha1 gene in chondroblasts requires the homeobox gene Dlx-2. DNA Cell Biol 20:359-65
Ji, X; Chen, D; Xu, C et al. (2000) Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A. J Bone Miner Metab 18:132-9
Yoneda, T (1998) Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone. Eur J Cancer 34:240-5
Nishimura, R; Moriyama, K; Yasukawa, K et al. (1998) Combination of interleukin-6 and soluble interleukin-6 receptors induces differentiation and activation of JAK-STAT and MAP kinase pathways in MG-63 human osteoblastic cells. J Bone Miner Res 13:777-85
Xu, C; Ji, X; Harris, M A et al. (1998) A clonal chondrocytic cell line derived from BMP-2/T antigen-expressing transgenic mouse. In Vitro Cell Dev Biol Anim 34:359-63
Reddy, S V; Roodman, G D (1998) Control of osteoclast differentiation. Crit Rev Eukaryot Gene Expr 8:1-17
Chen, D; Ji, X; Harris, M A et al. (1998) Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages. J Cell Biol 142:295-305
Roodman, G D (1998) Osteoclast differentiation and activity. Biochem Soc Trans 26:7-13
Mundy, G R (1997) Growth factors as potential therapeutic agents in osteoporosis. Instr Course Lect 46:495-8
Cody, J D; Singer, F R; Roodman, G D et al. (1997) Genetic linkage of Paget disease of the bone to chromosome 18q. Am J Hum Genet 61:1117-22

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