| pubmed-article:21068439 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0001675 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0026809 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0026336 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0521324 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0795693 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0205082 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C1335280 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C1706044 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C1527148 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:21068439 | lifeskim:mentions | umls-concept:C0243067 | lld:lifeskim |
| pubmed-article:21068439 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:21068439 | pubmed:dateCreated | 2011-3-1 | lld:pubmed |
| pubmed-article:21068439 | pubmed:abstractText | SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations. | lld:pubmed |
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| pubmed-article:21068439 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21068439 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21068439 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21068439 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21068439 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21068439 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:21068439 | pubmed:issn | 1754-8411 | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:MishinaYujiY | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:FengGen-Sheng... | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:WilkinsonJohn... | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:KamiyaNobuhir... | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:KingPhilip... | lld:pubmed |
| pubmed-article:21068439 | pubmed:author | pubmed-author:LapinskiPhili... | lld:pubmed |
