PUBLICATION

Melatonin suppresses both osteoblast and osteoclast differentiation through repression of epidermal Erk signaling in the zebrafish scale

Authors
Kobayashi-Sun, J., Suzuki, N., Hattori, A., Yamaguchi, M., Kobayashi, I.
ID
ZDB-PUB-200810-29
Date
2020
Source
Biochemical and Biophysical Research Communications   530(4): 644-650 (Journal)
Registered Authors
Kobayashi, Isao
Keywords
Melatonin, Osteoblasts, Osteoclasts, Scale, Zebrafish
MeSH Terms
  • Animal Scales/cytology
  • Animal Scales/drug effects
  • Animal Scales/physiology
  • Animals
  • Cell Differentiation/drug effects
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Fracture Healing/drug effects
  • MAP Kinase Signaling System/drug effects*
  • Melatonin/pharmacology*
  • Osteoblasts/cytology
  • Osteoblasts/drug effects*
  • Osteoclasts/cytology
  • Osteoclasts/drug effects*
  • Osteogenesis/drug effects*
  • Zebrafish/physiology
PubMed
32768192 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Melatonin has been implicated in the regulation of bone metabolism; however, the molecular mechanisms underlying its involvement in fracture healing are still obscure. We previously developed an in vivo fracture healing model using the scale of a double-transgenic zebrafish, trap:GFP; osterix:mCherry, which labels osteoclasts and osteoblasts with GFP and mCherry, respectively. Here we show using this model that melatonin inhibits both osteoblast and osteoclast differentiation under fracture stress through the repression of Erk signaling in epidermal cells of the scale. Melatonin treatment resulted in reduced numbers of both osteoblasts and osteoclasts in the fractured scale. Immunochemistry analysis revealed that Erk signals in epidermal cells, which express melatonin receptors, were greatly enhanced in response to fracture stress, but this enhancement was blocked by melatonin treatment. Moreover, inhibition of Erk signaling phenocopied the effects of melatonin treatment in the fractured scale. Collectively, these data suggest that the activation of epidermal Erk signaling is required for both osteoblast and osteoclast differentiation in the early stage of fracture healing, and melatonin suppresses epidermal Erk signaling, leading to impaired fracture healing.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping