TREM2 and β-Catenin Regulate Bone Homeostasis by Controlling the Rate of Osteoclastogenesis
| Autor: | F. Patrick Ross, Haibo Zhao, Steve L. Teitelbaum, Susan Gilfillan, Marina Cella, Karel Otero, Hiroshi Takayanagi, Roberta Faccio, Marco Colonna, Masahiro Shinohara, Angela Colucci |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Beta-catenin
Cellular differentiation Blotting Western Immunology Fluorescent Antibody Technique Osteoclasts Biology Article Bone and Bones Mice Osteoclast medicine Animals Homeostasis Immunoprecipitation Immunology and Allergy Receptors Immunologic beta Catenin Cell Proliferation Mice Knockout Membrane Glycoproteins Microglia Reverse Transcriptase Polymerase Chain Reaction TREM2 Stem Cells Cell Differentiation Cell biology Mice Inbred C57BL medicine.anatomical_structure Catenin biology.protein Female Stem cell |
| Zdroj: | The Journal of Immunology. 188:2612-2621 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1102836 |
| Popis: | TREM2 is an immunoreceptor expressed on osteoclasts (OC) and microglia that transmits intracellular signals through the adaptor DAP12. Individuals with genetic mutations inactivating TREM2 or DAP12 develop the Nasu–Hakola disease (NHD) with cystic-like lesions of the bone and brain demyelination that lead to fractures and presenile dementia. The mechanisms of this disease are poorly understood. In this study, we report that TREM2-deficient mice have an osteopenic phenotype reminiscent of NHD. In vitro, lack of TREM2 impairs proliferation and β-catenin activation in osteoclast precursors (OcP) in response to M-CSF. This defect results in accelerated differentiation of OcP into mature OC. Corroborating the importance of a balanced proliferation and differentiation of OcP for bone homeostasis, we show that conditional deletion of β-catenin in OcP also results in reduced OcP proliferation and accelerated osteoclastogenesis in vitro as well as osteopenia in vivo. These results reveal that TREM2 regulates the rate of osteoclastogenesis and provide a mechanism for the bone pathology in NHD. |
| Databáze: | OpenAIRE |
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