PUBLICATION

Hedgehog signaling regulates osteoblast differentiation in zebrafish larvae through modulation of autophagy

Authors
Hu, Z., Chen, B., Zhao, Q.
ID
ZDB-PUB-190418-16
Date
2019
Source
Biology Open   8(5): (Journal)
Registered Authors
Keywords
Atg5, Autophagy, BMP2, Gli2, Hh signaling, Mineralization, Osteoblast, Ptch1, SHH, Zebrafish
Datasets
GEO:GSE120170
MeSH Terms
none
PubMed
30992325 Full text @ Biol. Open
Abstract
Impaired osteoblast differentiation may result in bone metabolic disease such as osteoporosis. It was reported recently that Hedgehog (Hh) signaling and autophagy are two important regulators of bone differentiation. In order to further dissect their relationship in bone development, we used a zebrafish larvae model to investigate how disruption of one of these signaling affects the function of another and impacts osteoblast differentiation. Our results showed that activation of Hh signaling negatively regulated autophagy. However, suppression of autophagy by knocking down atg5 expression didn't alter Hh signaling, but dramatically up-regulated the expression of osteoblast related genes and increased bone mineralization especially in den region. On the contrary, inhibition of Hh signaling pathway by cyclopamine treatment suppressed the expression of osteoblast related genes and decreased bone mineralization. In agreement with these findings, blocking Hh signaling through knock down SHH and Gli2 genes led to defective osteoblast differentiation, while promoting Hh signaling by knock down Ptch1 was beneficial to osteoblast differentiation. Our results thus support that activation of Hh signaling pathway negatively regulates autophagy and consequentially promotes osteoblast differentiation. On the contrary, induction of autophagy inhibits osteoblast differentiation. Our work revealed the mechanism underlying Hh signaling pathway regulation of bone development.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ck3TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    gli2aMO4-gli2aMRPHLNO
    ptch1MO4-ptch1MRPHLNO
    shhaMO7-shhaMRPHLNO
    1 - 3 of 3
    Show
    Fish
    No data available
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-bmp2/4monoclonal
      IgG1Mouse
      Ab2-sp7polyclonal
        IgGGoat
        Ab4-atg5polyclonalRabbit
        Ab4-sqstm1polyclonalRabbit
        Ab8-map1lc3bmonoclonal
          IgG2aMouse
          1 - 5 of 5
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
          Show
          Mapping
          No data available