Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3.

摘要: From birth, the vault of skull grows at a prodigious rate, driven by activity osteoblastic cells fibrous joints (sutures) that separate bony calvarial plates. One in 2500 children is born with medical condition known as craniosynostosis because premature fusion plates and cessation bone growth sutures. Bone morphogenetic proteins (BMPs) are potent factors promote formation. Previously, we found Glypican-1 (GPC1) Glypican-3 (GPC3) expressed cranial sutures decreased during suture children. Although glypicans to regulate BMP signalling, mechanistic link between GPC1, GPC3 BMPs osteogenesis has not yet been investigated. We now report human primary mesenchymal coexpress GPC1 on cell surface release them into media. show they inhibit BMP2, BMP4 BMP7 activities, which both physically interact BMP2 immunoblockade endogenous potentiates activity. In contrast, increased levels result overexpression or addition recombinant protein, signalling BMP2-mediated osteogenesis. demonstrate mediated SMAD-dependent SMAD-independent pathways pathways. inhibition independent attachment glypican post-translational glycanation, thus appears be core protein. The discovery osteogenesis, responsiveness cells, indicates how downregulation expression could lead characterizes craniosynostosis.