Transglutaminase modification of the matrix through promotion of calcification

Transglutaminases have been identified for more than 60 years, but it was not until recently that the functions of these enzymes began to be understood. Currently, transglutaminases are accepted to be modulators of both osteoblastic and chondrocytic mineralization. This review details recent findings regarding this action of transglutaminases, primarily transglutaminase-2 and factor XIIIA, in both physiologic and pathologic mineralization of bone and cartilage. Osteoblast and chondrocyte mineralization is stimulated by the presence of extracellular factor XIIIA or transglutaminase-2. Specifically, the binding of transglutaminase-2 to GTP is critical for maximal induction of type X collagen expression and matrix calcification in articular chondrocytes. Furthermore, these enzymes can modulate collagen expression and therefore the related terminal cell differentiation events. Finally recent work suggests that transglutaminases are responsible for modifying other proteins to promote mineral deposition. The mechanism of transglutaminase-induced mineralization is critical to our understanding and potential modulation of pathologic mineralization events. Elucidation of these events could promote new disease-modifying therapies for the hypertrophic differentiation and mineralization found in osteoarthritic cartilage as well as other soft tissue calcification disorders.