This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnson, K. Articles by Terkeltaub, R. Search for Related Content PubMed PubMed Citation Articles by Johnson, K. Articles by Terkeltaub, R.

(American Journal of Pathology. 2001;159:149-163.)
© 2001 American Society for Investigative Pathology

Regular Articles

Interleukin-1 Induces Pro-Mineralizing Activity of Cartilage Tissue Transglutaminase and Factor XIIIa

Kristen Johnson^*, Sanshiro Hashimoto, Martin Lotz, Kenneth Pritzker and Robert Terkeltaub^*

From the Department of Medicine,^*
Rheumatology Allergy-Immunology Division, Veterans Affairs Medical Center, University of California at San Diego, La Jolla, California; the Division of Molecular Medicine,
The Scripps Research Institute, La Jolla, California; and the Department of Pathology,
Mount Sinai Hospital, University of Toronto, Toronto, Canada

Two transglutaminases (TGases), Factor XIIIa and tissue TGase (tTGase), are expressed in temporal-spatial association with matrix calcification in growth plates. Meniscal and articular cartilage matrix calcification are prevalent in osteoarthritis (OA) and aging. Here, we demonstrated up-regulation of tTGase and Factor XIIIa in superficial and deep zones of knee OA articular cartilage and the central (chondrocytic) zone of OA menisci. Transforming growth factor-ß and interleukin (IL)-1ß induced Factor XIIIa and tTGase expression in cartilage and meniscal organ cultures. Thus, we studied TGase activity. Donor age-dependent, OA severity-related, and IL-1-induced increases in TGase activity were demonstrated in both knee menisci and cultured meniscal cells. Meniscal cell TGase activity was stimulated by nitric oxide donors and tumor necrosis factor-, but transforming growth factor-ß did not stimulate TGase activity. The iNOS inhibitor N-monomethylarginine (NMMA) and an inhibitor of tumor necrosis factor receptor-associated factor (TRAF)2 and TRAF6 signaling (the zinc finger protein A20) suppressed IL-1 induction of TGase activity. Increased Factor XIIIa and tTGase activities, achieved via direct transfection of chondrocytic TC28 and meniscal cells, both induced matrix apatite deposition. Thus, Factor XIIIa and tTGase activities were increased in aging, degenerative cartilages and induced by IL-1. Because TGase activity promoted apatite deposition, our findings potentially implicate inflammation in the pathogenesis of cartilage matrix calcification.

This article has been cited by other articles:

				A-M Sims, A E Timms, J Bruges-Armas, R Burgos-Vargas, C-T Chou, T Doan, A Dowling, R N Fialho, P Gergely, D D Gladman, et al. Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis Ann Rheum Dis, September 1, 2008; 67(9): 1305 - 1309. [Abstract] [Full Text] [PDF]

				K. A. Johnson, D. M. Rose, and R. A. Terkeltaub Factor XIIIA mobilizes transglutaminase 2 to induce chondrocyte hypertrophic differentiation J. Cell Sci., July 1, 2008; 121(13): 2256 - 2264. [Abstract] [Full Text] [PDF]

				D. L. Cecil and R. Terkeltaub Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes J. Immunol., June 15, 2008; 180(12): 8378 - 8385. [Abstract] [Full Text] [PDF]

				K. A. Johnson, M. Polewski, and R. A. Terkeltaub Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells Circ. Res., March 14, 2008; 102(5): 529 - 537. [Abstract] [Full Text] [PDF]

				S. G. Priglinger, C. S. Alge, D. Kook, M. Thiel, R. Schumann, K. Eibl, A. Yu, A. S. Neubauer, A. Kampik, and U. Welge-Lussen Potential role of tissue transglutaminase in glaucoma filtering surgery. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3835 - 3845. [Abstract] [Full Text] [PDF]

				W.A. Boisvert, D.M. Rose, A. Boullier, O. Quehenberger, A. Sydlaske, K.A Johnson, L.K. Curtiss, and R. Terkeltaub Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 563 - 569. [Abstract] [Full Text] [PDF]

				M.T. Kaartinen, W. Sun, N. Kaipatur, and M.D. McKee Transglutaminase Crosslinking of SIBLING Proteins in Teeth Journal of Dental Research, July 1, 2005; 84(7): 607 - 612. [Abstract] [Full Text] [PDF]

				K. A. Johnson and R. A. Terkeltaub External GTP-bound Transglutaminase 2 Is a Molecular Switch for Chondrocyte Hypertrophic Differentiation and Calcification J. Biol. Chem., April 15, 2005; 280(15): 15004 - 15012. [Abstract] [Full Text] [PDF]

				D. Merz, R. Liu, K. Johnson, and R. Terkeltaub IL-8/CXCL8 and Growth-Related Oncogene {alpha}/CXCL1 Induce Chondrocyte Hypertrophic Differentiation J. Immunol., October 15, 2003; 171(8): 4406 - 4415. [Abstract] [Full Text] [PDF]

				S. S. Akimov and A. M. Belkin Opposing Roles of Ras/Raf Oncogenes and the MEK1/ERK Signaling Module in Regulation of Expression and Adhesive Function of Surface Transglutaminase J. Biol. Chem., September 12, 2003; 278(37): 35609 - 35619. [Abstract] [Full Text] [PDF]

				K. A. Johnson, D. van Etten, N. Nanda, R. M. Graham, and R. A. Terkeltaub Distinct Transglutaminase 2-independent and Transglutaminase 2-dependent Pathways Mediate Articular Chondrocyte Hypertrophy J. Biol. Chem., May 23, 2003; 278(21): 18824 - 18832. [Abstract] [Full Text] [PDF]

				S. G. Priglinger, C. A. May, A. S. Neubauer, C. S. Alge, C.-L. Schonfeld, A. Kampik, and U. Welge-Lussen Tissue Transglutaminase as a Modifying Enzyme of the Extracellular Matrix in PVR Membranes Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 355 - 364. [Abstract] [Full Text] [PDF]