Linked Life Data

7512387

Source:http://linkedlifedata.com/resource/pubmed/id/7512387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-5-13
pubmed:abstractText
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies characterised by synovial proliferation and non-inflammatory degradation of intra-articular collagenous structures. BCP crystals stimulate fibroblast and chondrocyte mitogenesis, metalloprotease secretion and prostaglandin production. As a tissue protective effect of prostaglandins has been suggested, we recently studied the effect of PGE1 on BCP crystal-induced mitogenesis and collagenase mRNA accumulation in human fibroblasts (HF). We demonstrated a dose-dependent inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation. The mechanism of PGE1 inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation was therefore explored. PGE1 (100 ng/ml) increased HF intracellular cAMP 40-fold over control. BCP alone caused no such change but inhibited the PGE1-induced increase in intracellular cAMP by at least 60%. The PGE1-induced increase in intracellular cAMP was also blocked by the adenyl cyclase inhibitor, 2',5'-dideoxyadenosine (ddA) (10 microM) and ddA reversed the PGE1-mediated inhibition of BCP crystal-induced mitogenesis. Dibutyryl cAMP also inhibited BCP crystal-induced mitogenesis in a concentration-dependent manner. Agents which increase intracellular cAMP levels such as the adenyl cyclase activator forskolin and the phosphodiesterase, inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effect of PGE1 on HF collagenase mRNA levels. PGE1 inhibits the biologic effects of BCP crystals through the cAMP signal transduction pathway and such inhibition may have significant therapeutic implications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine, http://linkedlifedata.com/resource/pubmed/chemical/Alprostadil, http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Collagenases, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Dideoxyadenosine, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins E, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/alpha-tricalcium phosphate, http://linkedlifedata.com/resource/pubmed/chemical/calcium phosphate, http://linkedlifedata.com/resource/pubmed/chemical/dicalcium phosphate anhydrous, http://linkedlifedata.com/resource/pubmed/chemical/monocalcium phosphate, http://linkedlifedata.com/resource/pubmed/chemical/tetracalcium phosphate
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
1226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-104
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
The role of cyclic-3',5'-adenosine monophosphate in prostaglandin-mediated inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase induction in cultured human fibroblasts.
pubmed:affiliation
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't