Bone morphogenetic proteins: from developmental signals to tissue regeneration

Abstract

The Sixth International Conference on Bone Morphogenetic Proteins took place between 11 and 15 October 2006 in Cavtat, Croatia, and was organized by the Croatian Calcified Tissues Society and Zagreb School of Medicine. ![][1] At present, bone is the only human organ that can be fully regenerated by exogenously applied bone morphogenetic proteins (BMPs) when physiological mechanisms of fracture repair fail. Since the identification of BMPs (Urist, 1965; Sampath & Reddi, 1981; Wozney et al , 1988; Ozkaynak et al , 1990; Chang et al , 1994), there have been many scientific discoveries and clinical reports on their use (reviewed by Vukicevic & Sampath, 2004). More than 340,000 patients worldwide have been successfully treated with recombinant BMPs for long‐bone non‐unions, acute fractures and spinal fusions. At the Sixth International Conference on Bone Morphogenetic Proteins, the roles of BMPs in signal transduction, developmental biology, metabolic bone diseases, joint and cartilage repair, skeleton reconstruction, kidney regeneration and tumour biology were discussed by leading experts in the field. BMPs are dimeric molecules that induce signalling through a heterotetrameric receptor complex composed of two type I and two type II serine–threonine kinase receptors, known as BMP receptors (BMPRs). The mode of BMPR oligomerization determines the resulting BMPR signal. Binding of BMPs to preformed heteromeric receptor complexes activates the nuclear effector proteins known as Smads, whereas binding to the high‐affinity type I receptor and recruitment of the low‐affinity type II receptor induces a Smad‐independent signalling pathway (Miyazono et al , 2005). After BMP‐induced heterodimeric complex formation, the constitutively active type II receptor kinase phosphorylates the type I receptor and subsequently activates intracellular signalling by phosphorylating downstream components (Fig 1). The BMP ligand connects the receptors—which otherwise have no contact between their ectodomains—and induces allosteric changes. W. Sebald (Wurzburg, Germany) showed that BMP2 acts as a rigid … [1]: /embed/graphic-1.gif