Abstract

The differentiation of osteoclasts (OCs) is dependent upon critical signals provided by two molecules: osteoprotegerin (OPGL) and macrophage colony stimulating factor (M-CSF). The binding of M-CSF to its receptor (c-fms) results in phosphorylation of tyrosine residues in the cytoplasmic portion of the receptor, generating downstream signals. Although structure-function analyses of c-fms have been carried out previously in other cell types, these studies have yielded conflicting results. In addition, there is question whether results obtained with other cell types can be extrapolated to c-fms signaling in OCs. This proposal will therefore determine the tyrosine residues critical for osteoclast (OC) survival, proliferation and differentiation of OC precursors, and the function of mature OCs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046852-03
Application #
6512188
Study Section
Special Emphasis Panel (ZRG1-OBM-2 (02))
Program Officer
Sharrock, William J
Project Start
2000-05-08
Project End
2003-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
3
Fiscal Year
2002
Total Cost
$202,461
Indirect Cost

  Institution

Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110

  Publications

Bush, Jason A; Kitaura, Hideki; Ma, Yuliang et al. (2012) Comparative proteomic analysis of a cytosolic fraction from ?3 integrin-deficient cells. Cancer Genomics Proteomics 9:1-13
Croke, Monica; Ross, F Patrick; Korhonen, Matti et al. (2011) Rac deletion in osteoclasts causes severe osteopetrosis. J Cell Sci 124:3811-21
Kim, Hyun-Ju; Warren, Julia T; Kim, Shin-Yoon et al. (2010) Fyn promotes proliferation, differentiation, survival and function of osteoclast lineage cells. J Cell Biochem 111:1107-13
Kim, Hyun-Ju; Zou, Wei; Ito, Yuji et al. (2010) Src-like adaptor protein regulates osteoclast generation and survival. J Cell Biochem 110:201-9
Morgan, Elizabeth A; Schneider, Jochen G; Baroni, Timothy E et al. (2010) Dissection of platelet and myeloid cell defects by conditional targeting of the beta3-integrin subunit. FASEB J 24:1117-27
Ito, Yuji; Teitelbaum, Steven L; Zou, Wei et al. (2010) Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL/M-CSF signaling and osteoclast polarization. J Clin Invest 120:1981-93
Kim, Hyun-Ju; Zhang, Kaihua; Zhang, Lihong et al. (2009) The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 106:2325-30
Reeve, Jennifer L; Zou, Wei; Liu, Yuli et al. (2009) SLP-76 couples Syk to the osteoclast cytoskeleton. J Immunol 183:1804-12
Zou, Wei; Reeve, Jennifer L; Zhao, Haibo et al. (2009) Syk tyrosine 317 negatively regulates osteoclast function via the ubiquitin-protein isopeptide ligase activity of Cbl. J Biol Chem 284:18833-9
Bai, Shuting; Kopan, Raphael; Zou, Wei et al. (2008) NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 283:6509-18

Showing the most recent 10 out of 36 publications