Impaired differentiation of osteoclasts in TREM-2-deficient individuals.
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.
Cella
Marina
M
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Buonsanti
Cecilia
C
Strader
Carey
C
Kondo
Takayuki
T
Salmaggi
Andrea
A
Colonna
Marco
M
D000199:Actins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000502:physiology; D023461:Myeloid Progenitor Cells / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D018003:Receptors, Calcitonin / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013577:Syndrome; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D000199:Actins; D039302:Integrin alphaVbeta3; D008562:Membrane Glycoproteins; D018003:Receptors, Calcitonin; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C498715:TREM2 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor