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PMID: 12913093 Published · ppublish English Journal Article

Impaired differentiation of osteoclasts in TREM-2-deficient individuals.

The Journal of experimental medicine ·Vol. 198 ·No. 4 ·2003-08-18 ·Pages 645-51

Cella M, Buonsanti C, Strader C, Kondo T, Salmaggi A, Colonna M

Abstract

TREM-2 is an immunoglobulin-like cell surface receptor associated with DAP12/KARAP that activates monocyte-derived dendritic cells (DCs) in vitro. Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease. This observation suggests that TREM-2 may function in myeloid cells other than DCs, most probably osteoclasts (OCs) and microglial cells, which are involved in bone modeling and brain function. Consistent with this prediction, here we show that OC differentiation is dramatically arrested in TREM-2-deficient patients, resulting in large aggregates of immature OCs that exhibit impaired bone resorptive activity. These results demonstrate a critical role for TREM-2 in the differentiation of mononuclear myeloid precursors into functional multinucleated OCs.

MeSH Terms
Actins/metabolism Cell Differentiation/physiology Granulocyte-Macrophage Colony-Stimulating Factor/metabolism Humans Integrin alphaVbeta3/metabolism Interleukin-4/metabolism Macrophage Colony-Stimulating Factor/metabolism Membrane Glycoproteins/genetics,metabolism Monocytes/physiology Myeloid Progenitor Cells/physiology Osteoclasts/cytology,physiology Receptors, Calcitonin/metabolism Receptors, Immunologic/genetics,metabolism Syndrome Triggering Receptor Expressed on Myeloid Cells-1
Chemicals
Actins Integrin alphaVbeta3 Membrane Glycoproteins Receptors, Calcitonin Receptors, Immunologic TREM1 protein, human TREM2 protein, human Triggering Receptor Expressed on Myeloid Cells-1 Interleukin-4 Macrophage Colony-Stimulating Factor Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cella Marina
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Buonsanti Cecilia
Strader Carey
Kondo Takayuki
Salmaggi Andrea
Colonna Marco
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20022220
Published
2003-08-18
Epub
2003-00-11
Pages
645-51
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194167
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20022220 PMC Full Text View journal details
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