Linked Life Data

11856642

Source:http://linkedlifedata.com/resource/pubmed/id/11856642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-3-7
pubmed:abstractText
Mucopolysaccharidosis type VII (MPS VII) is a heritable lysosomal storage disease caused by a deficiency in beta-glucuronidase (GUSB) activity, leading to progressive accumulation of undegraded glycosaminoglycans in many tissues. Clinical features include growth and mental retardation, hearing and visual defects, shortened lifespan, and skeletal deformities. A murine model of MPS VII has been described that shares many of the manifestations of the human disease, including the skeletal dysplasia. In this study we describe abnormalities in the cellular morphology and function of osteoclasts and a localized defect in bone formation rate in the MPS VII mouse. Ultrastructural analysis revealed that MPS VII osteoclasts fail to form ruffled border membranes and many appeared to be detached from the bone surface. Following bone marrow transplantation, osteoclasts derived from wild-type donors showed normal morphology and were closely associated with the bone surface in MPS VII recipients. In vitro bone resorption assays demonstrated that MPS VII osteoclasts formed significantly smaller and fewer pits than those formed by osteoclasts derived from normal mice of the same strain. Although osteoclast morphology and function appeared to be abnormal in the MPS VII mouse, interleukin-1 (IL-1)-induced osteoclastogenesis in vivo was not affected. In addition to the osteoclast defects, MPS VII mice demonstrated a slower rate of bone matrix deposition in the epiphysis by in vivo calcein labeling experiments. These data suggest that abnormal morphology and function of MPS VII osteoclasts, combined with deficient matrix deposition, may contribute to the skeletal defects observed in this lysosomal storage disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
8756-3282
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
352-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Abnormal osteoclast morphology and bone remodeling in a murine model of a lysosomal storage disease.
pubmed:affiliation
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't