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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2005-6-6
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pubmed:abstractText |
Loss of function mutations in the gene encoding the heparan sulfate proteoglycan Glypican-3 (GPC3) causes an X-linked disorder in humans known as Simpson-Golabi-Behmel Syndrome (SGBS). This disorder includes both pre- and postnatal overgrowth, a predisposition to certain childhood cancers, and a complex assortment of congenital defects including skeletal abnormalities. In this study, we have identified a previously unrecognized delay in endochondral ossification associated with the loss of Gpc3 function. Gpc3 knockout animals show a marked reduction in calcified trabecular bone, and an abnormal persistence of hypertrophic chondrocytes at embryonic day 16.5 (E16.5). These hypertrophic chondrocytes down-regulate Type X collagen mRNA expression and undergo apoptosis, suggesting a normal progression of hypertrophic chondrocyte cell fate. However, replacement of these cells by mineralized bone is delayed in association with a marked delay in the appearance of osteoclasts in the bone in vivo. This delay in vivo correlates with a significant reduction in the capacity to form osteoclasts from bone marrow macrophage precursors in vitro in response to M-CSF and RANKL, and with a reduction in the numbers of bone-marrow-derived cells expressing the markers CD11b and Gr-1. Together, these results indicate selective impairment in the development of the common hematopoietic lineage from which monocyte/macrophages and PMNs are derived. This is the first report of a requirement for heparan sulfate, and specifically Gpc3, in the lineage-specific differentiation of these cell types in vivo.
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pubmed:grant |
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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/5-bromo-4-chloro-3-indolyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type X,
http://linkedlifedata.com/resource/pubmed/chemical/Galactosides,
http://linkedlifedata.com/resource/pubmed/chemical/Glypicans,
http://linkedlifedata.com/resource/pubmed/chemical/Heparan Sulfate Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf11a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf11 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0012-1606
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
152-62
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15936336-Animals,
pubmed-meshheading:15936336-Apoptosis,
pubmed-meshheading:15936336-Bone Marrow Cells,
pubmed-meshheading:15936336-Bromodeoxyuridine,
pubmed-meshheading:15936336-Carrier Proteins,
pubmed-meshheading:15936336-Cell Differentiation,
pubmed-meshheading:15936336-Chondrocytes,
pubmed-meshheading:15936336-Collagen Type X,
pubmed-meshheading:15936336-Flow Cytometry,
pubmed-meshheading:15936336-Galactosides,
pubmed-meshheading:15936336-Glypicans,
pubmed-meshheading:15936336-Hematopoiesis,
pubmed-meshheading:15936336-Heparan Sulfate Proteoglycans,
pubmed-meshheading:15936336-Immunohistochemistry,
pubmed-meshheading:15936336-In Situ Hybridization,
pubmed-meshheading:15936336-Indoles,
pubmed-meshheading:15936336-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:15936336-Membrane Glycoproteins,
pubmed-meshheading:15936336-Mice,
pubmed-meshheading:15936336-Mice, Knockout,
pubmed-meshheading:15936336-Mutation,
pubmed-meshheading:15936336-Osteoclasts,
pubmed-meshheading:15936336-Osteogenesis,
pubmed-meshheading:15936336-RANK Ligand,
pubmed-meshheading:15936336-Receptor Activator of Nuclear Factor-kappa B
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pubmed:year |
2005
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pubmed:articleTitle |
Altered hematopoiesis in glypican-3-deficient mice results in decreased osteoclast differentiation and a delay in endochondral ossification.
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pubmed:affiliation |
Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO 63110, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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