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001-es BibID:	BIBFORM038694
Első szerző:	Matta Csaba (molekuláris biológus, genetikus, angol szakfordító)
Cím:	Insights into the role of intracellular Ca2+ concentration changes during chondrogenesis / Csaba Matta, János Fodor, Tamás Juhász, Róza Zákány
Dátum:	2012
Megjegyzések:	It is well established that Ca2+ signalling mediates the effects of mechanotransduction in chondrocytes of mature articular cartilage. However, little is known about the precise regulation of Ca2+ homeostasis in differentiating cells of developing hyaline cartilage. Therefore, our research group is committed to characterise the Ca2+ homeostasis and to map the ♭Ca-toolkit' of differentiating chondrogenic mesenchymal cells. High density cell culture system (HDC) established from chondrogenic mesenchymal cells isolated from limb buds of 4-day-old chicken embryos is a well-known model of in vitro cartilage differentiation, in which a spontaneous cartilage formation occurs in 6 days. We measured cytosolic free Ca2+ concentration ([Ca2+]i) in cells of HDC on different days of culturing. After an initial value of 80 nM, a significant transient elevation was detected in Fura-2-loaded cells on day 3 of culturing, when the majority of cells differentiate into chondroblasts and chondrocytes. This 140 nM peak of cytosolic Ca2+ concentration is a result of increased Ca-influx and is found to be indispensable to proper chondrogenesis, because elimination of extracellular Ca2+ abolished the Ca2+ peak of day 3 and inhibited cartilage formation. Uncontrolled Ca2+ influx evoked by a Ca2+ ionophore (A23187) exerted dual effects on chondrogenesis in a concentration dependent manner; low concentration ionophore increased [Ca2+]i up to 150 nM and facilitated cartilage formation, whereas high concentration of this compound elevated it over 250 nM and almost totally blocked cartilage formation. Proliferation of chondrogenic cells was more sensitive to modulation of [Ca2+]i then the viability of cells. Although chondrogenic cells express both IP3 and ryanodine receptors and can release Ca2+ from intracellular stores, these stores proved to play a minor role in the Ca2+ homeostasis of these cells. As the inhibition of the Ca2+-calmodulin sensitive protein phosphatase calcineurin impeded the [Ca2+]i-peak in chondrogenic cells and reduced cartilage formation, we propose its contribution in the regulation of [Ca2+]i of these cells. We also found that chondrogenic cells secreted ATP and administration of ATP to the culture medium evoked Ca2+ transients exclusively in the presence of extracellular Ca2+ and on day 3 of culturing. Moreover, ATP caused elevated protein expression of the chondrogenic transcription factor Sox9 and also stimulated cartilage matrix production. ATP may exert these functions via acting through purinergic receptors; and indeed, expression of both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors were detected. Metabotropic purinergic receptor agonist UTP caused a low level (60 nM) transient elevation of [Ca2+]i in 3-day-old HDC, without having an influence on cartilage matrix production. Application of suramin, which blocks all P2X receptors but not P2X4 did not impede the effects of ATP; furthermore, P2X4 appeared in the plasma membrane of differentiating cells only from day 3. In summary, chondrogenic cells possess a set of different molecules which enable them to modulate their Ca2+ homeostasis and [Ca2+]i was found to be kept in a narrow range during chondrogenesis. We present evidence on a significant new regulatory mechanism of chondrogenesis with revealing the role of Ca-influx of chondrogenic cells via P2X4 purinergic receptors.
ISBN:	978-1-61324-313-8
Tárgyszavak:	Orvostudományok Elméleti orvostudományok könyvfejezet Ca-homeostasis chondrogenesis egyetemen (Magyarországon) készült közlemény
Megjelenés:	Calcium signaling / ed. Masayoshi Yamaguchi. - p. 131-147. -
További szerzők:	Fodor János (1973-) (élettanász, biotechnológus) Juhász Tamás (1976-) (biológus, orvosbiológus) Zákány Róza (1963-) (anatómus-, kötőszövetbiológus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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