Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Csaba Matta, János Fodor, Nicolai Miosge, Roland Takács, Tamás Juhász, Henrik Rybaltovszki, Adrienn Tóth, László Csernoch, Róza Zákány

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19 Citations (Scopus)

Abstract

Osteoarthritis (OA) is the most common form of chronic musculoskeletal disorders. A migratory stem cell population termed chondrogenic progenitor cells (CPC) with in vitro chondrogenic potential was previously isolated from OA cartilage. Since intracellular Ca2+ signalling is an important regulator of chondrogenesis, we aimed to provide a detailed understanding of the Ca2+ homeostasis of CPCs. In this work, CPCs immortalised by lentiviral administration of the human telomerase reverse transcriptase (hTERT) and grown in monolayer cultures were studied. Expressions of all three IP3Rs were confirmed, but no RyR subtypes were detected. Ca2+ oscillations observed in CPCs were predominantly dependent on Ca2+ release and store replenishment via store-operated Ca2+ entry; CPCs express both STIM1 and Orai1 proteins. Expressions of adenosine receptor mRNAs were verified, and adenosine elicited Ca2+ transients. Various P2 receptor subtypes were identified; P2Y1 can bind ADP; P2Y4 is targeted by UTP; and ATP may evoke Ca2+ transients via detected P2X subtypes, as well as P2Y1 and P2Y2. Enzymatic breakdown of extracellular nucleotides by apyrase completely abrogated Ca2+ oscillations, suggesting that an autocrine/paracrine purinergic mechanism may drive Ca2+ oscillations in these cells. As CPCs possess a broad spectrum of functional molecular elements of Ca2+ signalling, Ca2+-dependent regulatory mechanisms can be supposed to influence their differentiation potential.

Original languageEnglish
Pages (from-to)429-442
Number of pages14
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number2
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Calcium oscillation
  • Chondrogenesis
  • Mesenchymal stem cell
  • Osteoarthritis
  • SOCE

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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