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.
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18 August 2003
Brief Definitive Report|
August 11 2003
Impaired Differentiation of Osteoclasts in TREM-2–deficient Individuals
Marina Cella,
Marina Cella
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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Cecilia Buonsanti,
Cecilia Buonsanti
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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Carey Strader,
Carey Strader
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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Takayuki Kondo,
Takayuki Kondo
2Department of Neurology, Fukui Redcross Hospital, 2-4-1 Tsukimi Fukui 918-8501, Japan
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Andrea Salmaggi,
Andrea Salmaggi
3Department of Clinical Neurosciences, Istituto Nazionale Neurologico C. Besta, 20133 Milano, Italy
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Marco Colonna
Marco Colonna
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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Marina Cella
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Cecilia Buonsanti
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Carey Strader
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Takayuki Kondo
2Department of Neurology, Fukui Redcross Hospital, 2-4-1 Tsukimi Fukui 918-8501, Japan
Andrea Salmaggi
3Department of Clinical Neurosciences, Istituto Nazionale Neurologico C. Besta, 20133 Milano, Italy
Marco Colonna
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Address correspondence to Marco Colonna, Department of Pathology and Immunology, Washington University School of Medicine, West Building, Room 4724, Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: 314-362-0367; Fax: 314-362-4096; email: [email protected]
The online version of this article contains supplemental material.
Received:
December 26 2002
Revision Received:
May 27 2003
Accepted:
May 27 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (4): 645–651.
Article history
Received:
December 26 2002
Revision Received:
May 27 2003
Accepted:
May 27 2003
Citation
Marina Cella, Cecilia Buonsanti, Carey Strader, Takayuki Kondo, Andrea Salmaggi, Marco Colonna; Impaired Differentiation of Osteoclasts in TREM-2–deficient Individuals . J Exp Med 18 August 2003; 198 (4): 645–651. doi: https://doi.org/10.1084/jem.20022220
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