Osteogenic and Chondrogenic Master Genes Expression Is Dependent on the Kir2.1 Potassium Channel Through the Bone Morphogenetic Protein Pathway

Jonathan Pini, Serena Giuliano, Julia Matonti, Lila Gannoun, Dina Simkin, Matthieu Rouleau, Saïd Bendahhou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Andersen's syndrome is a rare disorder affecting muscle, heart, and bone that is associated with mutations leading to a loss of function of the inwardly rectifying K+ channel Kir2.1. Although the Kir2.1 function can be anticipated in excitable cells by controlling the electrical activity, its role in non-excitable cells remains to be investigated. Using Andersen's syndrome–induced pluripotent stem cells, we investigated the cellular and molecular events during the osteoblastic and chondrogenic differentiation that are affected by the loss of the Ik1 current. We show that loss of Kir2.1 channel function impairs both osteoblastic and chondrogenic processes through the downregulation of master gene expression. This downregulation is the result of an impairment of the bone morphogenetic proteins signaling pathway through dephosphorylation of the Smad proteins. Restoring Kir2.1 channel function in Andersen's syndrome cells rescued master genes expression and restored normal osteoblast and chondrocyte behavior. Our results show that Kir2.1-mediated activity controls endochondral and intramembranous ossification signaling pathways.

Original languageEnglish (US)
Pages (from-to)1826-1841
Number of pages16
JournalJournal of Bone and Mineral Research
Volume33
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • ANDERSEN'S SYNDROME
  • IPSC
  • OSTEOBLAST
  • OSTEOGENESIS
  • POTASSIUM CHANNELS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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