Your browser doesn't support javascript.
loading
Therapeutic effect of nanogel-based delivery of soluble FGFR2 with S252W mutation on craniosynostosis.
Yokota, Masako; Kobayashi, Yukiho; Morita, Jumpei; Suzuki, Hiroyuki; Hashimoto, Yoshihide; Sasaki, Yoshihiro; Akiyoshi, Kazunari; Moriyama, Keiji.
Afiliación
  • Yokota M; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • Kobayashi Y; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Hard Tissue Genome Research Center, Tokyo Medical and Dental Univers
  • Morita J; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • Suzuki H; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Hard Tissue Genome Research Center, Tokyo Medical and Dental Univers
  • Hashimoto Y; ERATO, Japan Science and Technology Agency, Tokyo, Japan.
  • Sasaki Y; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan; Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
  • Akiyoshi K; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan; Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan; ERATO, Japan Science and Technology Agency, Tokyo, Japan.
  • Moriyama K; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Hard Tissue Genome Research Center, Tokyo Medical and Dental Univers
PLoS One ; 9(7): e101693, 2014.
Article en En | MEDLINE | ID: mdl-25003957
Apert syndrome is an autosomal dominantly inherited disorder caused by missense mutations in fibroblast growth factor receptor 2 (FGFR2). Surgical procedures are frequently required to reduce morphological and functional defects in patients with Apert syndrome; therefore, the development of noninvasive procedures to treat Apert syndrome is critical. Here we aimed to clarify the etiological mechanisms of craniosynostosis in mouse models of Apert syndrome and verify the effects of purified soluble FGFR2 harboring the S252W mutation (sFGFR2IIIcS252W) on calvarial sutures in Apert syndrome mice in vitro. We observed increased expression of Fgf10, Esrp1, and Fgfr2IIIb, which are indispensable for epidermal development, in coronal sutures in Apert syndrome mice. Purified sFGFR2IIIcS252W exhibited binding affinity for fibroblast growth factor (Fgf) 2 but also formed heterodimers with FGFR2IIIc, FGFR2IIIcS252W, and FGFR2IIIbS252W. Administration of sFGFR2IIIcS252W also inhibited Fgf2-dependent proliferation, phosphorylation of intracellular signaling molecules, and mineralization of FGFR2S252W-overexpressing MC3T3-E1 osteoblasts. sFGFR2IIIcS252W complexed with nanogels maintained the patency of coronal sutures, whereas synostosis was observed where the nanogel without sFGFR2S252W was applied. Thus, based on our current data, we suggest that increased Fgf10 and Fgfr2IIIb expression may induce the onset of craniosynostosis in patients with Apert syndrome and that the appropriate delivery of purified sFGFR2IIIcS252W could be effective for treating this disorder.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Polietileneimina / Acrocefalosindactilia / Sistemas de Liberación de Medicamentos / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Polietileneimina / Acrocefalosindactilia / Sistemas de Liberación de Medicamentos / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos