title: Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone.
abstract: Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of recently developed anti-osteoporotic treatments. Two bone-specific transcription factors, RUNX2 and OSX, have been shown to interact and co-ordinately regulate the expression of bone-specific genes. Although it has been recently shown that sclerostin is targeted by OSX in mice, there is currently no information of whether this is also the case in human cells. We have identified SP-protein family and AML1 consensus binding sequences at the human SOST promoter and have shown that OSX, together with RUNX2, binds to a specific region close to the transcription start site. Furthermore, we show that OSX and RUNX2 activate SOST expression in a co-ordinated manner in vitro and that SOST expression levels show a significant positive correlation with OSX/RUNX2 expression levels in human bone. We also confirmed previous results showing an association of several SOST/RUNX2 polymorphisms with bone mineral density.
authors.affiliation: Faculty of Medicine Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors.forename: Flor M
authors.initials: FM
authors.lastname: Pérez-Campo
authors.affiliation: Unit of Legal Medicine, Faculty of Medicine, University of Cantabria, Santander, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Santurtún
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL, University of Cantabria, Avda. Valdecilla S/N, 39008, Santander, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ibarbia
authors.affiliation: Service of Traumatology and Orthopedic Surgery, Hospital U. Marqués de Valdecilla, University of Cantabria, Santander, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Pascual
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL, University of Cantabria, Avda. Valdecilla S/N, 39008, Santander, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Valero
authors.affiliation: Service of Traumatology and Orthopedic Surgery, Hospital U. Marqués de Valdecilla, University of Cantabria, Santander, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Garcés
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL, University of Cantabria, Avda. Valdecilla S/N, 39008, Santander, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sañudo
authors.affiliation: Unit of Legal Medicine, Faculty of Medicine, University of Cantabria, Santander, Spain.
authors.forename: María T
authors.initials: MT
authors.lastname: Zarrabeitia
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL, University of Cantabria, Avda. Valdecilla S/N, 39008, Santander, Spain. rianchoj@unican.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D000076182:Sp7 Transcription Factor / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D005819:Genetic Markers; C493709:RUNX2 protein, human; C422903:SOST protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human
keywords: Bone mineral density; Human; OSTERIX; Polymorphisms; RUNX; SOST; Sclerostin