Subtilisin-like proprotein convertase PACE4 (SPC4) is a candidate processing enzyme of bone morphogenetic proteins during tooth formation

The temporospatial expression of PACE4, a member of the mammalian subtilisi n-like proprotein convertase family, in the developing rat molar tooth was determined by in situ hybridization. At the initiation stage of tooth devel opment, PACE I, mRNA was weakly expressed in the dental lamina, whereas the mesenchymal cells intensely expressed the PACE4 transcript. At the bud sta ge, high-level expression of PACE4 mRNA was found in the dental epithelium and condensed dental mesenchyme. Its expression became more localized in th e differentiating ameloblasts during cap and early bell stages. In the newb orn rats, PACE4 mRNA was localized in the ameloblasts and odontoblasts, but its expression became weaker with advancing development, showing apparent association with the differentiation and establishment of functional amelob lasts and odontoblasts. These expression patterns of PACE4 were very simila r to those of several bone morphogenetic proteins (BMPs) reported previousl y, Because BMPs, which are primarily involved in the morphogenesis in tooth formation, are synthesized as inactive precursors and activated by limited proteolysis at the consensus Arg-X-X-Arg maturation site, the present obse rvations suggest that PACE4 is possibly a candidate proBMP convertase that acts during tooth formation, (C) 1999 Wiley-Liss, Inc.