title: Store-operated calcium entry and calcium influx via voltage-operated calcium channels regulate intracellular calcium oscillations in chondrogenic cells.
abstract: Chondrogenesis is known to be regulated by calcium-dependent signalling pathways in which temporal aspects of calcium homeostasis are of key importance. We aimed to better characterise calcium influx and release functions with respect to rapid calcium oscillations in cells of chondrifying chicken high density cultures. We found that differentiating chondrocytes express the α1 subunit of voltage-operated calcium channels (VOCCs) at both mRNA and protein levels, and that these ion channels play important roles in generating Ca(2+) influx for oscillations as nifedipine interfered with repetitive calcium transients. Furthermore, VOCC blockade abrogated chondrogenesis and almost completely blocked cell proliferation. The contribution of internal Ca(2+) stores via store-operated Ca(2+) entry (SOCE) seems to be indispensable to both Ca(2+) oscillations and chondrogenesis. Moreover, this is the first study to show the functional expression of STIM1/STIM2 and Orai1, molecules that orchestrate SOCE, in chondrogenic cells. Inhibition of SOCE combined with ER calcium store depletion abolished differentiation and severely diminished proliferation, suggesting the important role of internal pools in calcium homeostasis of differentiating chondrocytes. Finally, we present an integrated model for the regulation of calcium oscillations of differentiating chondrocytes that may have important implications for studies of chondrogenesis induced in various stem cell populations.
authors.affiliation: Department of Physiology, Medical and Health Science Centre, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Fodor
authors.forename: Csaba
authors.initials: C
authors.lastname: Matta
authors.forename: Tamás
authors.initials: T
authors.lastname: Oláh
authors.forename: Tamás
authors.initials: T
authors.lastname: Juhász
authors.forename: Roland
authors.initials: R
authors.lastname: Takács
authors.forename: Adrienn
authors.initials: A
authors.lastname: Tóth
authors.forename: Beatrix
authors.initials: B
authors.lastname: Dienes
authors.forename: László
authors.initials: L
authors.lastname: Csernoch
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D023421:Models, Animal; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D002118:Calcium