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The systemic effects of sclerostin overexpression using ΦC31 integrase in mice.
Zhang, Dongdong; Park, Bo Mi; Kang, Myengmo; Nam, HeeJin; Kim, Eun Jin; Bae, ChuHyun; Lim, Sung Kil.
Afiliación
  • Zhang D; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Division of Endocrinology & Metabolism, Department of Internal Medicine, Affiliated Yantai Hospital of Binzhou Medical University, Yantai, PR China.
  • Park BM; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
  • Kang M; Division of Endocrinology and Endocrine Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Nam H; Division of Endocrinology and Endocrine Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim EJ; Division of Endocrinology and Endocrine Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Bae C; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
  • Lim SK; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Division of Endocrinology and Endocrine Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: lsk@yuhs.ac.
Biochem Biophys Res Commun ; 472(3): 471-6, 2016 Apr 08.
Article en En | MEDLINE | ID: mdl-26845353
Sclerostin, encoded by the Sost gene, is mainly produced by osteocytes in bone and antagonizes the Wnt/ß-catenin signaling pathway, which is a requisite for bone formation. Currently, human anti-sclerostin antibodies are being tested in phase III clinical trials. In addition, serum sclerostin levels are reported to be associated with bone mineral density and fracture risk in normal individuals; however, the correlation between serum sclerostin and bone mass remains controversial. To study the effects of the continuous exposure of exogenous sclerostin on bone, a ΦC31 integrase system, which has the characteristics of site-specificity and efficiency, was applied for the delivery of the Sost gene in this study. We injected Sost-attB plasmid with or without ΦC31 integrase plasmid into the mouse tail vein using a hydrodynamic-based method. The site-specific integration of the Sost gene into the mouse genome was confirmed by examining a pseudo-attP site on the hepatic genomic DNA. Sclerostin was expressed in the hepatocytes, secreted into the blood flow, and maintained at high concentrations in the mice with both Sost-attB plasmid and ΦC31 integrase plasmid injections, which was observed by serial measurement. Moreover, the mice with long-term high levels of serum sclerostin showed trabecular bone loss on micro-CT analysis. Peripheral B cell populations were not affected. Our results suggested that sclerostin could be expressed in the liver and sustained successfully at high levels in the blood by using the ΦC31 integrase system, leading to trabecular bone loss. These findings may help to further ascertain the effects of sclerostin introduced exogenously on the skeleton.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Bacteriófagos / Huesos / Glicoproteínas / Integrasas Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Bacteriófagos / Huesos / Glicoproteínas / Integrasas Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos