Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-9-15
pubmed:abstractText
Proteolytic degradation of the major cartilage macromolecules, aggrecan and type II collagen, is a key pathological event in osteoarthritis (OA). ADAMTS-4 and ADAMTS-5, the primary aggrecanases capable of cartilage aggrecan cleavage, are synthesized as latent enzymes and require prodomain removal for activity. The N-termini of the mature proteases suggest that activation involves a proprotein convertase, but the specific family member responsible for aggrecanase activation in cartilage in situ has not been identified. Here we describe purification of a proprotein convertase activity from human OA cartilage. Through biochemical characterization and the use of siRNA, PACE4 was identified as a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage. Posttranslational activation of ADAMTS-4 and ADAMTS-5 was observed in the extracellular milieu of cartilage, resulting in aggrecan degradation. These findings suggest that PACE4 represents a novel target for the development of OA therapeutics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1096-0384
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
478
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-51
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Proprotein convertase activation of aggrecanases in cartilage in situ.
pubmed:affiliation
Pfizer Global Research and Development, 700 Chesterfield Parkway-AA3E, Chesterfield, St. Louis, MO 63017, USA. anne-marie.malfait@pfizer.com
pubmed:publicationType
Journal Article