Interleukin-1 induces pro-mineralizing activity of cartilage tissue transglutaminase and factor XIIIa

Two transglutaminases (TGases), Factor XIIIa and tissue TGase (tTGase), are expressed in temporal-spatial association with matrix calcification In gro wth plates. Meniscal and articular cartilage matrix calcification are preva lent in osteoarthritis (OA) and aging. Here, we demonstrated up-regulation of tTGase and Factor XIIIa in superficial and deep zones of knee OA articul ar cartilage and the central (chondrocytic) zone of OA menisci. Transformin g growth factor-beta and interleukin (IL)-1 beta Induced Factor XIIIa and t TGase 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 cul tured meniscal cells. Meniscal cell TGase activity was stimulated by nitric oxide donors and tumor necrosis factor-alpha, but transforming growth fact or-beta did not stimulate TGase activity. The iNOS inhibitor N-monomethylar ginine (NMMA) and an Inhibitor of tumor necrosis factor receptor-associated factor (TRAF)2 and TRAF6 signaling (the zinc finger protein A20) suppresse d IL-1 Induction of TGase activity. Increased Factor XIIIa and tTGase activ ities, achieved via direct transfection of chondrocytic TC28 and meniscal c ells, 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 pot entially implicate inflammation in the pathogenesis of cartilage matrix cal cification.