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Osteocyte Death and Bone Overgrowth in Mice Lacking Fibroblast Growth Factor Receptors 1 and 2 in Mature Osteoblasts and Osteocytes.
McKenzie, Jennifer; Smith, Craig; Karuppaiah, Kannan; Langberg, Joshua; Silva, Matthew J; Ornitz, David M.
Afiliación
  • McKenzie J; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
  • Smith C; Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Karuppaiah K; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • Langberg J; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • Silva MJ; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • Ornitz DM; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
J Bone Miner Res ; 34(9): 1660-1675, 2019 09.
Article en En | MEDLINE | ID: mdl-31206783
Fibroblast growth factor (FGF) signaling pathways have well-established roles in skeletal development, with essential functions in both chondrogenesis and osteogenesis. In mice, previous conditional knockout studies suggested distinct roles for FGF receptor 1 (FGFR1) signaling at different stages of osteogenesis and a role for FGFR2 in osteoblast maturation. However, the potential for redundancy among FGFRs and the mechanisms and consequences of stage-specific osteoblast lineage regulation were not addressed. Here, we conditionally inactivate Fgfr1 and Fgfr2 in mature osteoblasts with an Osteocalcin (OC)-Cre or Dentin matrix protein 1 (Dmp1)-CreER driver. We find that young mice lacking both receptors or only FGFR1 are phenotypically normal. However, between 6 and 12 weeks of age, OC-Cre Fgfr1/Fgfr2 double- and Fgfr1 single-conditional knockout mice develop a high bone mass phenotype with increased periosteal apposition, increased and disorganized endocortical bone with increased porosity, and biomechanical properties that reflect increased bone mass but impaired material properties. Histopathological and gene expression analyses show that this phenotype is preceded by a striking loss of osteocytes and accompanied by activation of the Wnt/ß-catenin signaling pathway. These data identify a role for FGFR1 signaling in mature osteoblasts/osteocytes that is directly or indirectly required for osteocyte survival and regulation of bone mass during postnatal bone growth. © 2019 American Society for Bone and Mineral Research.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteocitos / Desarrollo Óseo / Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Bone Miner Res Asunto de la revista: METABOLISMO / ORTOPEDIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteocitos / Desarrollo Óseo / Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Bone Miner Res Asunto de la revista: METABOLISMO / ORTOPEDIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos