Transglutaminases in bone formation and bone matrix stabilization

Bone is formed throughout a life span of an individual by osteoblasts in a process termed osteogenesis. Osteoblasts arise from mesenchymal stem cells and form type I collagen and plasma fibronectin rich extracellular matrix that mineralizes in the high phosphate concentration that is generated by alkaline phosphatase activity. Matrix quantity, quality and mineralization levels define the strength of bone. This chapter discusses the process of osteogenesis and the potential role of transglutaminases in this process. Osteoblasts express two transglutaminase enzymes, transglutaminase 2 and Factor XIII-A, which based on our current understanding appear to regulate osteoblast adhesion and their matrix deposition, respectively. Transglutaminase 2 acts on the cell surface and partners with FN (fibronectin) to promote integrin-mediated adhesion in a transamidase-independent manner. Factor XIII-A is mostly involved in promotion of extracellular matrix production and stabilization, the main substrate being plasma fibronectin. We will also briefly discuss the role of the enzymes in adipogenesis, the potential effect of serotonylation reaction to bone matrix quality and what transglutaminase mouse models have taught us on the enzymes in bone in vivo.