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

  • Signaling and cell physiology
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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.

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2-Aminoethoxydiphenyl borate


Arachidonic acid-regulated Ca2+ channel


Cyclopiazonic acid


Chondrogenic progenitor cell


Calcium release activated Ca2+ channel


Embryonic stem cell


Full time at half maximum


High density cell culture


Human telomerase reverse transcriptase


Inositol 1,2,3-trisphosphate receptor


Mesenchymal stem cell


Sodium calcium exchanger




Phosphate-buffered saline with Tween 20




Plasma membrane Ca2+-ATPase


Ryanodine receptor


Sodium dodecyl sulphate polyacrylamide gel electrophoresis


Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase


Store-operated Ca2+ entry


Stromal interacting molecule


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We are grateful to Mrs. Krisztina Bíró and Mrs. Róza Őri for the excellent and skillful technical assistance. This work was supported by grants from the Hungarian Science Research Fund (OTKA CNK80709, OTKA NN-107765), from TÁMOP-4.2.2.A-11/1/KONV-2012-0036 and TÁMOP-4.2.2/B-10/1-2010-0024 projects, co-financed by the European Union and the European Social Fund. N.M. was supported by the German Research Foundation (Mi 573/10-1). C.M. was supported by a Mecenatura grant (DEOEC Mec-9/2011) from the Medical and Health Science Centre, University of Debrecen, Hungary; a Short-Term Fellowship from the Federation of European Biochemical Societies (FEBS); and also from the European Union through a Marie Curie Intra-European Fellowship for career development (project number: 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF). This paper was supported by the János Bólyai Research Scholarship of the Hungarian Academy of Sciences. T.J. is supported by a Magyary Zoltán postdoctoral fellowship through the project entitled “National Excellence Program—Elaboration and implementation of a national student and researcher supporting system for the convergence region” (TÁMOP 4.2.4.A/2-11-1-2012-0001), co-financed by the Hungarian State, the European Union, and the European Social Fund.

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All authors disclose that there are neither any financial nor any personal relationships with other people or organisations that could inappropriately influence (bias) their work. There are no conflicts of interests.

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Correspondence to Róza Zákány.

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Csaba Matta and János Fodor contributed equally to the work.

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Matta, C., Fodor, J., Miosge, N. et al. Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells. Pflugers Arch - Eur J Physiol 467, 429–442 (2015).

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