Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
| Autor: | Tadatsugu Taniguchi, Eiji Kobayashi, Sunhwa Kim, Ayako Suematsu, Toshiyuki Takai, Hiroshi Takayanagi, Masanori Inui, Takako Koga, Kazuya Inoue, Toshio Iwata, Takashi Matozaki, Hiroshi Ohnishi, Tatsuhiko Kodama |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
musculoskeletal diseases
Macrophage colony-stimulating factor Osteoimmunology Amino Acid Motifs Fc receptor Osteoclasts Receptors Cell Surface Biology Bone and Bones Mice Osteoclast Osteogenesis medicine Animals Homeostasis Calcium Signaling Bone Resorption Receptors Immunologic Cells Cultured Adaptor Proteins Signal Transducing Multidisciplinary Membrane Glycoproteins Receptor Activator of Nuclear Factor-kappa B Macrophage Colony-Stimulating Factor RANK Ligand Receptors IgG Cell Differentiation Cell biology Adaptor Proteins Vesicular Transport medicine.anatomical_structure Biochemistry Nuclear receptor RANKL biology.protein Signal transduction Carrier Proteins Gene Deletion |
| Zdroj: | Nature. 428(6984) |
| ISSN: | 1476-4687 |
| Popis: | Costimulatory signals are required for activation of immune cells, but it is not known whether they contribute to other biological systems. The development and homeostasis of the skeletal system depend on the balance between bone formation and resorption. Receptor activator of NF-kappaB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF). But it remains unclear how RANKL activates the calcium signals that lead to induction of nuclear factor of activated T cells c1, a key transcription factor for osteoclastogenesis. Here we show that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harbouring adaptors, Fc receptor common gamma subunit (FcRgamma) and DNAX-activating protein (DAP)12, exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, FcRgamma and DAP12 associate with multiple immunoreceptors and activate calcium signalling through phospholipase Cgamma. Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis. |
| Databáze: | OpenAIRE |
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