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Transglutaminase contributes to CPPD crystal formation in osteoarthritis
David Heinkel1, Claudia M Gohr, Miwa Uzuki
1Division of Rheumatology, The Zablocki VA Medical Center and the Medical College of Wisconsin, 5000 W. National Avenue, Milwaukee, WI 53295-1000, USA.
Frontiers in Bioscience : a Journal and Virtual Library
|September 9, 2004
Summary
Transglutaminase (Tgase) activity is elevated in osteoarthritic cartilage and promotes calcium pyrophosphate dihydrate (CPPD) crystal formation. Inhibiting Tgase reduces CPPD crystal development, suggesting a therapeutic target for osteoarthritis.
Area of Science:
- Biochemistry
- Orthopedics
- Cell Biology
Background:
- Calcium pyrophosphate dihydrate (CPPD) crystals are prevalent in osteoarthritic joints, indicating a poor prognosis.
- Transglutaminase (Tgase) enzymes are linked to pathological mineralization in cartilage, but their direct role in CPPD formation in osteoarthritis is unclear.
Purpose of the Study:
- To investigate the in-vivo activity of Tgase in normal and osteoarthritic human cartilage.
- To explore the effect of Tgase inhibitors on CPPD crystal formation in normal chondrocytes.
Main Methods:
- Measurement of in-vivo Tgase activity in human osteoarthritic and normal cartilage.
- Quantification of Tgase-specific crosslinks using High-Performance Liquid Chromatography (HPLC).
- Immunohistochemical localization of Tgase crosslinks and in-vitro assessment of Tgase inhibitors on CPPD crystal formation.
Main Results:
- Tgase-specific crosslink levels were significantly higher in osteoarthritic cartilage (4.74 +/- 0.7 pmol/ng protein) compared to normal cartilage (1.55 +/- 0.3 pmol/ng protein).
- Tgase crosslinks were localized around chondrocytes in osteoarthritic cartilage, near potential CPPD crystal sites.
- Tgase inhibitors effectively suppressed CPPD crystal formation in an in-vitro model using porcine chondrocytes.
Conclusions:
- Elevated Tgase activity in osteoarthritic cartilage plays a role in CPPD crystal formation.
- Tgase inhibition presents a potential therapeutic strategy for managing CPPD crystal-related cartilage degeneration.