IMR Press / FBL / Volume 9 / Issue 6 / DOI: 10.2741/1477

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Transglutaminase contributes to CPPD crystal formation in osteoarthritis
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1 The Division of Rheumatology, The Zablocki VAMC and the Medical College of Wisconsin, Milwaukee, WI 53295
Academic Editor:Yubo Sun
Front. Biosci. (Landmark Ed) 2004, 9(6), 3257–3261; https://doi.org/10.2741/1477
Published: 1 September 2004
(This article belongs to the Special Issue Crystals-associated arthropathies and therapeutic development)
Abstract

Calcium pyrophosphate dihydrate (CPPD) crystals are common components of osteoarthritic joints and correlate with a poor prognosis. Transglutaminase (Tgase) enzymes have been implicated in pathologic mineralization in cartilage; yet, definitive studies linking Tgase activity to CPPD crystal formation in osteoarthritic articular cartilage are lacking. We measured in-vivo Tgase activity in osteoarthritic and normal human cartilage, and explored the effect of Tgase inhibitors on CPPD crystal formation by normal chondrocytes. Osteoarthritic articular cartilage from was obtained from specimens discarded at the time of knee replacement surgery. Normal adult cartilage samples from a tissue bank were used as controls. Tgase-specific isopeptide (epsilon-(gamma-glutamyl) lysine) bonds were measured in cartilage extracts by HPLC. Tgase-specific crosslinks were localized in osteoarthritic cartilage by immunohistochemistry. The effect of Tgase inhibition was determined in an in-vitro model of CPPD crystal formation. Tgase-specific crosslink levels were 1.55 ± 0.3 picomoles/ng protein in normal human adult articular cartilage and 4.74 ± 0.7 picomoles/ng protein in osteoarthritic human cartilage (p < 0.001). Immunostaining confirmed the presence of Tgase crosslinks in the pericellular matrix of chondrocytes at potential sites of CPPD crystal formation. Tgase inhibitors suppressed CPPD crystal formation by porcine chondrocytes. These findings support a role for Tgase in CPPD crystal formation in aging or degenerated cartilage.

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