Linked Life Data

15569620

Source:http://linkedlifedata.com/resource/pubmed/id/15569620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-11-30
pubmed:abstractText
Phosphocitrate [PC] is a powerful inhibitor of biological crystallization and a potential disease modifying drug for crystal associated diseases such as crystals associated osteoarthritis [OA]. Recently, it has been reported that a new PC complex salt, calcium sodium PC [CaNaPC], is much more powerful than its precursor, sodium PC [NaPC], in reducing the size of chemically-induced calcified plaques in rat when examined using a calcergy assay (1). The molecular mechanisms underlying such a superior activity as a calcification inhibitor over its precursor NaPC are currently unknown. In order to evaluate the potential of CaNaPC as a disease modifying drug for crystals associated OA, we examined and compared CaNaPC and its precusor NaPC using several cell- based assays. CaNaPC was found to have an inhibitory potency similar to that of NaPC toward preventing the stimulating effects of basic calcium phosphate [BCP] crystals on the induction of MMP1, thymidine uptake and endocytosis. However, CaNaPC proved much more powerful than NaPC in the inhibition of amorphous calcium phosphate-DNA coprecipitates-induced cell death. These results suggest that the superior anti-calcification activity of NaCaPC over NaPC observed in rat is probably due to its superior activity in the inhibition of the effects associated with amorphous calcium phosphate clusters/aggregates/precipitates but not the effects associated with BCP crystals. Since amorphous calcium phosphate clusters/aggregates/precipitates are precursors of BCP crystals and coexist with calcium-containing crystals in calcified tissues (2-6), these amorphous clusters/aggregates/precipitates, similar to BCP crystals, may have played a significant role in pathological calcifications and in the development of crystals associated diseases such as crystals associated OA. The superior activity of CaNaPC over its precursor NaPC in the inhibition of amorphous calcium phosphate-DNA coprecipitates-induced cell death may, at least in part, explain its powerful anti-calcification activity in vivo. The findings suggest that CaNaPC through a dual action of inhibiting both the detrimental biological effects of formed BCP crystals and preforming amorphous calcium phosphate clusters/aggregates/precipitates, could present as a better disease-modifying drug for crystals associated OA than its parent NaPC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1093-4715
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
803-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibition of calcium phosphate-DNA coprecipitates induced cell death by phosphocitrates.
pubmed:affiliation
Rheumatology and Immunology, University of Miami School of Medicine, Miami, Florida 33101, USA. y.sun@miami.edu <y.sun@miami.edu>
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural