Abstract
RANKL induces the formation of osteoclasts, which are responsible for bone resorption. Herein we investigate the role of the transmembrane adaptor proteins in RANKL-induced osteoclastogenesis. LAT positively regulates osteoclast differentiation and is up-regulated by RANKL via c-Fos and NFATc1, whereas LAB and LIME act as negative modulators of osteoclastogenesis. In addition, silencing of LAT by RNA interference or overexpression of a LAT dominant negative in bone marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation. Furthermore, LAT is involved in RANKL-induced PLC(γ) activation and NFATc1 induction. Thus, our data suggest that LAT acts as a positive regulator of RANKL-induced osteoclastogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Bone Marrow Cells / cytology
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Cell Differentiation / genetics*
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Cells, Cultured
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Gene Expression Regulation, Developmental*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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NFATC Transcription Factors / genetics
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NFATC Transcription Factors / metabolism
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Osteoclasts* / cytology
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Osteoclasts* / metabolism
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Phospholipase C gamma / genetics
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Phospholipase C gamma / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Proto-Oncogene Proteins c-fos / deficiency
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Proto-Oncogene Proteins c-fos / genetics
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RANK Ligand / genetics
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RANK Ligand / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Lat protein, mouse
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Membrane Proteins
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NFATC Transcription Factors
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Nfatc1 protein, mouse
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Phosphoproteins
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Proto-Oncogene Proteins c-fos
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RANK Ligand
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Tnfsf11 protein, mouse
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Phospholipase C gamma