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rdf:type |
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lifeskim:mentions |
umls-concept:C0008029,
umls-concept:C0021368,
umls-concept:C0026809,
umls-concept:C0029453,
umls-concept:C0079784,
umls-concept:C0205217,
umls-concept:C0871261,
umls-concept:C0887899,
umls-concept:C1367028,
umls-concept:C1420022,
umls-concept:C1524003,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-12
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pubmed:abstractText |
While studies of the adaptor SH3BP2 have implicated a role in receptor-mediated signaling in mast cells and lymphocytes, they have failed to identify its function or explain why SH3BP2 missense mutations cause bone loss and inflammation in patients with cherubism. We demonstrate that Sh3bp2 "cherubism" mice exhibit trabecular bone loss, TNF-alpha-dependent systemic inflammation, and cortical bone erosion. The mutant phenotype is lymphocyte independent and can be transferred to mice carrying wild-type Sh3bp2 alleles through mutant fetal liver cells. Mutant myeloid cells show increased responses to M-CSF and RANKL stimulation, and, through mechanisms of increased ERK 1/2 and SYK phosphorylation/activation, they form macrophages that express high levels of TNF-alpha and osteoclasts that are unusually large. M-CSF and RANKL stimulation of myeloid cells that overexpress wild-type SH3BP2 results in similar large osteoclasts. This indicates that the mutant phenotype reflects gain of SH3BP2 function and suggests that SH3BP2 is a critical regulator of myeloid cell responses to M-CSF and RANKL stimulation.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11b,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Sh3bp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0092-8674
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pubmed:author |
pubmed-author:AgataNaokiN,
pubmed-author:EbiharaTakeshiT,
pubmed-author:KawaiToshihisaT,
pubmed-author:LinChin-YuCY,
pubmed-author:MukherjeePadma MPM,
pubmed-author:OlsenBjorn RBR,
pubmed-author:OnjiMasahiroM,
pubmed-author:ReichenbergerErnstE,
pubmed-author:SahekiYasunoriY,
pubmed-author:SenooMakotoM,
pubmed-author:UekiYasuyoshiY
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
128
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
71-83
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:17218256-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17218256-Animals,
pubmed-meshheading:17218256-Antigens, CD11b,
pubmed-meshheading:17218256-Arginine,
pubmed-meshheading:17218256-Bone Marrow Cells,
pubmed-meshheading:17218256-Bone Resorption,
pubmed-meshheading:17218256-Cell Differentiation,
pubmed-meshheading:17218256-Cherubism,
pubmed-meshheading:17218256-Disease Models, Animal,
pubmed-meshheading:17218256-Hematologic Diseases,
pubmed-meshheading:17218256-Homozygote,
pubmed-meshheading:17218256-Inflammation,
pubmed-meshheading:17218256-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17218256-Lymph Nodes,
pubmed-meshheading:17218256-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:17218256-Mice,
pubmed-meshheading:17218256-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17218256-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17218256-Mutation,
pubmed-meshheading:17218256-Myeloid Cells,
pubmed-meshheading:17218256-Osteoclasts,
pubmed-meshheading:17218256-Phosphorylation,
pubmed-meshheading:17218256-Proline,
pubmed-meshheading:17218256-Protein-Tyrosine Kinases,
pubmed-meshheading:17218256-RANK Ligand,
pubmed-meshheading:17218256-Spleen,
pubmed-meshheading:17218256-Tumor Necrosis Factor-alpha
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pubmed:year |
2007
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pubmed:articleTitle |
Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice.
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pubmed:affiliation |
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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