Journal article
The enigmatic function of TREM-2 in osteoclastogenesis
Advances in experimental medicine and biology, Vol.602, pp.97-105
2007
DOI: 10.1007/978-0-387-72009-8_13
PMID: 17966394
Abstract
The triggering receptor expressed on myeloid cells 2 (TREM-2) is a member of family of receptors that play a central role in regulating function of myeloid cells. TREM-2 is expressed on macrophages, microglia and pre-osteoclasts and transduces intracellular signals through the adaptor DAP12. In human, genetic defects of TREM-2 and DAP12 result in a rare syndrome characterized by presenile dementia and bone cysts. This syndrome and the tissue distribution of TREM-2 have indicated a role of the TREM-2/DAP12 complex in brain function and bone modeling, particularly osteoclastogenesis. Accordingly, human TREM-2- and DAP12-deficient pre-osteoclast precursors failed to differentiate in vitro into mature osteoclasts endowed with bone resorptive activity. In mouse, DAP12-deficiency also resulted in impaired osteoclastogenesis in vitro and a mild osteopetrosis in vivo although bone cysts were not observed. Surprisingly, TREM-2-deficiency in mouse led to accelerated osteoclastogenesis in vitro without osteopetrosis or bone cysts in vivo, revealing an unexpected inhibitory function of mouse TREM-2. These data demonstrate that TREM-2 function is essential for normal osteoclastogenesis. The conflicting results as to the relationship between TREM-2, DAP12 and osteoclastogenesis and bone modeling in human and mouse suggest that TREM-2 contribution to osteoclast biology may vary depending on the influence of additional DAP12-associated receptors and on the presence of TREM-2 ligands with variable avidity/affinity, which may induce either activating or an inhibitory signals through TREM-2/DAP12.
Details
- Title: Subtitle
- The enigmatic function of TREM-2 in osteoclastogenesis
- Creators
- Marco Colonna - Washington University School of Medicine, St. Louis, Department of Pathology and Immunology, MO, USA. mcolonna@pathology.wustl.eduIsaiah TurnbullJulia Klesney-Tait
- Resource Type
- Journal article
- Publication Details
- Advances in experimental medicine and biology, Vol.602, pp.97-105
- DOI
- 10.1007/978-0-387-72009-8_13
- PMID
- 17966394
- eISBN
- 9780387720098; 038772009X
- ISSN
- 0065-2598
- eISSN
- 2214-8019
- Language
- English
- Date published
- 2007
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094605702771
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