Linked Life Data

15094116

Source:http://linkedlifedata.com/resource/pubmed/id/15094116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-4-19
pubmed:abstractText
Pseudoachondroplasia (PSACH) is a well-characterized dwarfing condition associated with disproportionate short stature, abnormal joints and osteoarthritis requiring joint replacement. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP). COMP, the fifth member of the thrombospondin (TSP) gene family, is a pentameric protein found primarily in the extracellular matrix of musculoskeletal tissues. Functional studies have shown that COMP binds types II and IX collagens but the role of COMP in the extracellular matrix remains to be defined. Mutations in COMP interfere with calcium-binding and protein conformation. PSACH growth plate and growth plate chondrocytes studies indicate that COMP mutations have a dominant negative effect with both COMP and type IX collagen being retained in large rER cisternae. This massive retention causes impaired chondrocyte function with little COMP secreted into the matrix and premature loss of chondrocytes. Deficiency of linear growth results from loss of chondrocytes from the growth plate. Secondarily, the matrix contains minimal COMP, which may be normal and/or mutant, and little type IX collagen. This deficiency results in abnormal joints that are easily eroded and cause painful osteoarthritis. Unlike other misfolded proteins that are targeted for degradation, much of the retained COMP escapes degradation, compromises cell function, and causes cell death. Gene therapy will need to target the reduction of COMP in order to restore normal chondrocyte function and longevity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1357-2725
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1005-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Role of TSP-5/COMP in pseudoachondroplasia.
pubmed:affiliation
Department of Pediatrics, Medical School at Houston, University of Texas Health Science Center, 6431 Fannin, Room MSB 3.306, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't