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Specific inhibition of basic calcium phosphate and calcium pyrophosphate crystal-induction of metalloproteinase synthesis by phosphocitrate

Citation

Cheung, HS and Sallis, JD and Struve, JA, Specific inhibition of basic calcium phosphate and calcium pyrophosphate crystal-induction of metalloproteinase synthesis by phosphocitrate, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1315, (2) pp. 105-111. ISSN 0925-4439 (1996) [Refereed Article]

DOI: doi:10.1016/0925-4439(95)00106-9

Abstract

Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystal deposition diseases are a group of heterogeneous arthritides which are a significant source of morbidity in the elderly. Both crystals induced mitogenesis and metalloproteinase (MP) synthesis and secretion by fibroblasts and chondrocytes which may promote degradation of intra-articular tissue. We have previously shown that phosphocitrate (PC), an inhibitor of hydroxyapatite crystallization, specifically blocks BCP crystal-induced mitogenesis in 3T3 cells. This led us to examine the effect of PC on BCP and CPPD crystal induction of MP synthesis in human fibroblasts. PC (10-3 to 10-4 M) specifically inhibited the crystal-induced collagenase and stromelysin mRNA accumulation while having no effect on epidermal growth factor-induced or basal levels of mRNA for both enzymes. Western blots (collagenase) of conditioned media confirmed that PC blocked crystal-induced proteinase secretion as well. Moreover, PC (10-3 M) also blocked the crystal induction of c-fos and c-jun. Since FOS and JUN proteins form a transacting activator (AP-1) for expression of collagenase and stromelysin genes, PC may block the synthesis of both enzymes by inhibiting the transcription of c-fos and c-jun.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Rheumatology and Arthritis
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Sallis, JD (Dr John Sallis)
ID Code:6463
Year Published:1996
Web of Science® Times Cited:32
Deposited By:Biochemistry
Deposited On:1995-08-01
Last Modified:2011-08-25
Downloads:0

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