GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:15936336

From GONUTS
Jump to: navigation, search
Citation

Viviano, BL, Silverstein, L, Pflederer, C, Paine-Saunders, S, Mills, K and Saunders, S (2005) Altered hematopoiesis in glypican-3-deficient mice results in decreased osteoclast differentiation and a delay in endochondral ossification. Dev. Biol. 282:152-62

Abstract

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.

Links

PubMed Online version:10.1016/j.ydbio.2005.03.003

Keywords

Animals; Apoptosis/physiology; Bone Marrow Cells/metabolism; Bone Marrow Cells/physiology; Bromodeoxyuridine; Carrier Proteins/pharmacology; Cell Differentiation/physiology; Chondrocytes/metabolism; Collagen Type X/metabolism; Flow Cytometry; Galactosides; Glypicans; Hematopoiesis/genetics; Hematopoiesis/physiology; Heparan Sulfate Proteoglycans/genetics; Heparan Sulfate Proteoglycans/metabolism; Immunohistochemistry; In Situ Hybridization; Indoles; Macrophage Colony-Stimulating Factor/pharmacology; Membrane Glycoproteins/pharmacology; Mice; Mice, Knockout; Mutation/genetics; Osteoclasts/cytology; Osteoclasts/physiology; Osteogenesis/drug effects; Osteogenesis/physiology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GPC3

acts_upstream_of_or_within

GO:0030316: osteoclast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2159355

P

  • occurs_in:(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000092)

Seeded From UniProt

complete

MOUSE:GPC3

acts_upstream_of_or_within

GO:0030282: bone mineralization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2159355

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.