RRC ID 43940
Author Watanabe T, Tamamura Y, Hoshino A, Makino Y, Kamioka H, Amagasa T, Yamaguchi A, Iimura T.
Title Increasing participation of sclerostin in postnatal bone development, revealed by three-dimensional immunofluorescence morphometry.
Journal Bone
Abstract Confocal immunofluorescence tiling imaging revealed the spatio-temporal distributions of osterix and sclerostin in femurs from 3-day-old, 2-week-old and 4-week-old rats to be reciprocally exclusive at the tissue level. Further quantitative three-dimensional immuno fluorescence morphometry demonstrated the increasing distribution of sclerostin in the osteocytic lacuno-canalicular system specifically in diaphysis, which paralleled the cooperative participation and depletion of osterix and β-catenin in adjacent periosteum cells. Treating MC3T3-E1 cells with BIO (a GSK3 inhibitor) induced the stabilization of β-catenin and nuclear translocation of osterix, and negatively regulated osteocalcin/BGLAP and Dmp1. These results collectively demonstrate that the increasing distribution of sclerostin in diaphyseal cortical bone appears to be involved in the attenuation of osterix and β-catenin in adjacent periosteum cells, thus possibly contributing to osteoblast maturation and reducing the osteoblast formation at this bone site. Our confocal microscopy-based imaging analyses provide a comprehensive and detailed view of the spatio-temporal distribution of sclerostin, β-catenin and osterix at the tissue to subcellular level in a coherent manner, and uncovered their spatio-temporal cooperation in postnatal bone development, thus providing evidence that they link skeletogenic growth and functional bone development.
Volume 51(3)
Pages 447-58
Published 2012-9
DOI 10.1016/j.bone.2012.06.019
PII S8756-3282(12)00946-5
PMID 22766096
MeSH Aging / metabolism Animals Animals, Newborn Bone Development* / drug effects Bone Morphogenetic Proteins / metabolism* Cell Count Cell Line Cell Nucleus / drug effects Cell Nucleus / metabolism Core Binding Factor Alpha 1 Subunit / metabolism Diaphyses / cytology Diaphyses / drug effects Diaphyses / growth & development Diaphyses / metabolism Femur / cytology Femur / drug effects Femur / growth & development Femur / metabolism Fluorescent Antibody Technique / methods* Genetic Markers Imaging, Three-Dimensional / methods* Indoles / pharmacology Male Mice Microscopy, Confocal Osteocytes / cytology Osteocytes / drug effects Osteocytes / metabolism Oximes / pharmacology Protein Stability / drug effects Protein Transport / drug effects Rats Sp7 Transcription Factor Time Factors Transcription Factors / metabolism Wnt Signaling Pathway / drug effects beta Catenin / metabolism
IF 4.36
Times Cited 8
Human and Animal Cells