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MARK FAHEY, ELIZABETH MITTON, EMILY MUTH, and ANN K. ROSENTHAL 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 Dxm-induced 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. (J Rheumatol First Release Dec 15 2008; doi:10.3899/jrheum.080528) Key Indexing Terms: DEXAMETHASONE CHONDROCYTES CALCIUM PYROPHOSPHATE DIHYDRATE OSTEOARTHRITIS TRANSGLUTAMINASES From the Department of Medicine/Division of Rheumatology, Medical College of Wisconsin, and the Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, USA. Supported by National Institutes of Health grants AG-015337 (AKR) and a VA Merit Review grant. M. Fahey, BS, Laboratory Technologist; E. Mitton, MS, Senior Laboratory Technologist; E. Muth, BS, Laboratory Technologist; A.K. Rosenthal, MD, Professor of Medicine, Medical College of Wisconsin. Address reprint requests to Dr. A.K. Rosenthal, Rheumatology Section, cc-111W, Zablocki VA Medical Center, 5000 W. National Ave., Milwaukee, WI 53295-1000. E-mail: akrose@mcw.edu Accepted for publication August 11, 2008. |
