Discovery and biology of the SOST geneDiscovery and biology of the SOST gene
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Medical genetics of obesity and skeletal disorders (MGENOS)
Bologna :Medimond, 2008[*]2008
Proceedings of the 13th International Congress of Endocrinology, November 8-12, 2008, Rio de Janeiro, Brazil / Godoy Matos, A. [edit.]; et al. [edit.]
University of Antwerp
Positional cloning efforts on two clinically related sclerosing bone dysplasias, van Buchem disease and sclerosteosis resulted in the identification of the previously unknown SOST gene encoding sclerostin. The recessive mode of inheritance in combination with the loss of function mutations found, suggests a function as an inhibitor of bone formation. Expression studies showed a very restricted expression almost limited to the osteocytes. More recently, functional analysis revealed a role as an extracellular antagonist of canonical writ signalling by binding to the LDL receptor-related protein (LRP)-5. Canonical writ signalling was shown to be one of the key pathways in bone formation. The bone-specific expression pattern of sclerostin makes it a promising target to intervene into this pathway thus developing an anabolic treatment for osteoporosis and osteoporotic fractures.