Medical College of Wisconsin
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Dexamethasone promotes calcium pyrophosphate dihydrate crystal formation by articular chondrocytes. J Rheumatol 2009 Jan;36(1):163-9

Date

01/10/2009

Pubmed ID

19132782

Pubmed Central ID

PMC2640436

DOI

10.3899/jrheum.080528

Scopus ID

2-s2.0-58149526653 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) crystals are commonly found in osteoarthritic joints and correlate with a poor prognosis. Intraarticular corticosteroids, such as dexamethasone (Dxm), are commonly used therapies for osteoarthritis with or without CPPD deposition. Dxm has variable effects in mineralization models. We investigated the effects of Dxm on CPPD crystal formation in a well established tissue culture model.

METHODS: Porcine articular chondrocytes were incubated with ATP to generate CPPD crystals. Chondrocytes incubated with or without ATP were exposed to 1-100 nM Dxm in the presence of 45Ca. Mineralization was measured by 45Ca uptake in the cell layer. We also investigated the effect of Dxm on mineralization-regulating enzymes such as alkaline phosphatase, nucleoside triphosphate pyrophosphohydrolase (NTPPPH), and transglutaminase.

RESULTS: Dxm significantly increased ATP-induced mineralization by articular chondrocytes. While alkaline phosphatase and NTPPPH activities were unchanged by Dxm, transglutaminase activity increased in a dose-responsive manner. Levels of Factor XIIIA mRNA and protein were increased by Dxm, while type II Tgase protein was unchanged. Transglutaminase inhibitors suppressed Dxminduced increases in CPPD crystal formation.

CONCLUSION: These findings suggest a potential for Dxm to contribute to pathologic mineralization in cartilage and reinforce a central role for the transglutaminase enzymes in CPPD crystal formation.

Author List

Fahey M, Mitton E, Muth E, Rosenthal AK

Author

Ann K. Rosenthal MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium Pyrophosphate
Calcium Radioisotopes
Cartilage, Articular
Cells, Cultured
Chondrocalcinosis
Chondrocytes
Crystallization
Dexamethasone
Glucocorticoids
Swine
Teprotide
Transglutaminases