Type

Journal Article

Authors

G M McCarthy
D J Fitzgerald
J O'Byrne
B McDonnell
G A Doherty
M P Morgan
E S Molloy

Subjects

Biochemistry

Topics
crystallization matrix metalloproteinase 13 reverse transcriptase polymerase chain reaction cells cultured drug effects extracellular signal regulated map kinases humans fibroblasts receptors prostaglandin e calcium phosphate p38 mitogen activated protein kinases genetics signal transduction metabolism enzymology up regulation ptger2 protein human bafilomycin a1 cycloheximide osteoarthritis pathology dinoprostone physiology pharmacology receptors prostaglandin e ep4 subtype ptger4 protein human enzyme inhibitors gene expression regulation enzymologic macrolides synovial membrane nf kappa b calcium phosphates receptors prostaglandin e ep2 subtype

Mechanism of basic calcium phosphate crystal-stimulated matrix metalloproteinase-13 expression by osteoarthritic synovial fibroblasts: inhibition by prostaglandin E2. (2008)

Abstract To determine the mechanism of matrix metalloproteinase (MMP)-13 upregulation in osteoarthritic synovial fibroblasts (OASF) in response to stimulation with basic calcium phosphate (BCP) crystals and to investigate the effect of prostaglandin (PG)E2 on BCP crystal-stimulated MMP expression. Primary OASF were stimulated with BCP crystals; mRNA expression was measured by real-time reverse transcription-polymerase chain reaction and protein levels were assessed by Western blotting. BCP crystals upregulated MMP-13 mRNA expression over 20-fold and increased MMP-13 protein production in OASF. BCP crystal-stimulated MMP-13 mRNA expression was blocked by inhibition of the extracellular regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (MAPK) pathways and inhibition of the activation of nuclear factor kappaB. Addition of exogenous PGE2 downregulated BCP crystal-stimulated MMP-13 expression. In contrast, PGE2 upregulated, and had no effect, on BCP crystal stimulated MMP-3 and MMP-1 mRNA expression, respectively. These effects of PGE2 were diminished by L-161,982, a selective EP4 receptor antagonist, and mimicked by CAY10399, a selective EP2 receptor agonist, and forskolin, an adenylate cyclase activator. These data suggest that BCP crystal induction of MMP-13 expression may involve the ERK1/2 and p38 MAPK pathways and activation of nuclear factor kappaB; this upregulation of MMP-13 may contribute to the accelerated cartilage breakdown in BCP crystal-associated osteoarthritis. PGE2 had contrasting effects on BCP crystal-stimulated MMP-3 and MMP-13 mRNA expression, mediated in an EP2/EP4/cAMP-dependent manner, suggesting that PGE2 may have beneficial as well as deleterious effects in BCP crystal-associated osteoarthritis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

G M McCarthy, D J Fitzgerald, J O'Byrne, B McDonnell, G A Doherty, M P Morgan, E S Molloy

Experts in our system

1
Geraldine M McCarthy
University College Dublin
Total Publications: 38
 
2
D J Fitzgerald
Royal College of Surgeons in Ireland
Total Publications: 101
 
3
John M O'Byrne
Royal College of Surgeons in Ireland
Total Publications: 18
 
4
Glen A Doherty
University College Dublin
Total Publications: 57
 
5
Maria P Morgan
Royal College of Surgeons in Ireland
Total Publications: 27
 
6
Eamonn S Molloy
Royal College of Surgeons in Ireland
Total Publications: 7