Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation

Sci Rep. 2014 Jun 11:4:5066. doi: 10.1038/srep05066.

Abstract

The ZHTc6-MyoD embryonic stem cell line expresses the myogenic transcriptional factor MyoD under the control of a tetracycline-inducible promoter. Following induction, most of the ZHTc6-MyoD cells differentiate to myotubes. However, a small fraction does not differentiate, instead forming colonies that retain the potential for myocyte differentiation. In our current study, we found that parathyroid hormone type 1 receptor (PTH1R) expression in colony-forming cells at 13 days after differentiation was higher than that in the undifferentiated ZHTc6-MyoD cells. We also found that PTH1R expression was required for myocyte differentiation, and that parathyroid hormone accelerated the differentiation. Our analysis of human and mouse skeletal muscle tissues showed that most cells expressing PTH1R also expressed Pax7 and CD34, which are biomarkers of satellite cells. Furthermore, we found that parathyroid hormone treatment significantly improved muscle weakness in dystrophin-deficient mdx mice. This is the first report indicating that PTH1R and PTH accelerate myocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Line
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / physiology
  • Humans
  • Mice
  • Mice, Inbred mdx
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / physiology*
  • MyoD Protein / metabolism
  • PAX7 Transcription Factor / metabolism
  • Parathyroid Hormone / metabolism*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / physiology
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / metabolism
  • Satellite Cells, Skeletal Muscle / physiology
  • Tetracycline / pharmacology

Substances

  • Antigens, CD34
  • Biomarkers
  • MyoD Protein
  • PAX7 Transcription Factor
  • Parathyroid Hormone
  • Receptor, Parathyroid Hormone, Type 1
  • Tetracycline