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Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342.
Guo, Yue; Tang, Chen-Yi; Man, Xiao-Fei; Tang, Hao-Neng; Tang, Jun; Wang, Fang; Zhou, Ci-La; Tan, Shu-Wen; Feng, Yun-Zhi; Zhou, Hou-De.
Afiliação
  • Guo Y; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Tang CY; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Man XF; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Tang HN; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Tang J; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Wang F; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Zhou CL; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Tan SW; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
  • Feng YZ; Department of Stomatology, The Second Xiangya Hospital, Central South University, Hunan, China.
  • Zhou HD; Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and houdezhou@csu.edu.cn.
FASEB J ; 30(12): 4214-4226, 2016 12.
Article em En | MEDLINE | ID: mdl-27623927
Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1's role in the bone metabolism, we generated Irs-1-deficient Irs-1smla/smla mice. These null mice developed a spontaneous mutation that led to an increase in trabecular thickness (Tb.Th) in 12-mo-old, but not in 2-mo-old mice. Analyses of the bone marrow stromal cells (BMSCs) from these mice revealed their differential expression of osteogenesis-related genes and miRNAs. The expression of miR-342, predicted and then proven to target the gene encoding collagen type Iα2 (COL1A2), was reduced in BMSCs derived from Irs-1-null mice. COL1A2 expression was then shown to be age dependent in osteoblasts and BMSCs derived from Irs-1smla/smla mice. After the induction of osteogenesis in BMSCs, miR-342 expression correlated inversely with that of Col1a2 Further, Col1a2-specific small interfering RNA (siRNA) reduced alkaline phosphatase (ALP) activity and inhibited BMSC differentiation into osteocyte-like cells, both in wild-type (WT) and Irs-1smla/smla mice. Conversely, in Irs-1smla/smla osteocytes overexpressing COL1A2, ALP-positive staining was stronger than in WT osteocytes. In summary, we uncovered a temporal regulation of BMSC differentiation/bone formation, controlled via Irs-1/miR-342 mediated regulation of Col1a2 expression.-Guo, Y., Tang, C.-Y., Man, X.-F., Tang, H.-N., Tang, J., Wang, F., Zhou, C.-L., Tan, S.-W., Feng, Y.-Z., Zhou, H.-D. Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Células da Medula Óssea / Colágeno Tipo I / MicroRNAs / Proteínas Substratos do Receptor de Insulina / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Células da Medula Óssea / Colágeno Tipo I / MicroRNAs / Proteínas Substratos do Receptor de Insulina / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article