title: A Sclerostin super-producer cell line derived from the human cell line SaOS-2: a new tool for the study of the molecular mechanisms driving Sclerostin expression.
abstract: Sclerostin, the product of the SOST gene, is a key regulator of bone homeostasis. Sclerostin interferes with the Wnt signalling pathway and, therefore, has a negative effect on bone formation. Although the importance of sclerostin in bone homeostasis is well established, many aspects of its biology are still unknown. Due to its restricted pattern of expression, in vitro studies of SOST gene regulation are technically challenging. Furthermore, a more profound investigation of the molecular mechanism controlling sclerostin expression has been hampered by the lack of a good human in vitro model. Here, we describe two cell lines derived from the human osteosarcoma cell line SaOS-2 that produce elevated levels of sclerostin. Analysis of the super-producer cell lines showed that sclerostin levels were still reduced in response to parathyroid hormone treatment or in response to mechanical loading, indicating that these regulatory mechanisms were not affected in the presented cell lines. In addition, we did not find differences between the promoter or ECR5 sequences of our clones and the SaOS-2 parental line. However, the methylation of the proximal CpG island located at the SOST promoter was lower in the super-producer clones, in agreement with a higher level of SOST transcription. Although the underlying biological causes of the elevated levels of sclerostin production in this cell line are not yet clear, we believe that it could be an extremely useful tool to study the molecular mechanisms driving sclerostin expression in humans.
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL University of Cantabria, Avda. Valdecilla S/N, 39008, Santander, Cantabria, Spain.
authors.forename: Flor M
authors.initials: FM
authors.lastname: Pérez-Campo
authors.forename: Carolina
authors.initials: C
authors.lastname: Sañudo
authors.forename: Jesús
authors.initials: J
authors.lastname: Delgado-Calle
authors.forename: Jana
authors.initials: J
authors.lastname: Arozamena
authors.forename: María T
authors.initials: MT
authors.lastname: Zarrabeitia
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor / Q000378:metabolism*; D005819:Genetic Markers; D006801:Humans; D015151:Immunoblotting; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000502:physiology; D012516:Osteosarcoma; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human