N-methyl-D-aspartate (NMDA) receptor expression and function is required for early chondrogenesis

Cell Communication and Signaling

Csaba Matta¹  Róza Zákány¹  Tamás Juhász¹  Tibor Hajdú¹  Judit Vágó¹  Éva Katona¹  Csilla Szűcs-Somogyi¹  Roland Takács¹  Zoltan Varga²  Gyorgy Panyi²  Ádám Bartók²  János Fodor³  Tamás Oláh³  László Csernoch³ 

[1] Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen;Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen;Department of Physiology, Faculty of Medicine, University of Debrecen;

关键词: Chondrogenesis;    Chondrocyte;    N-methyl-D-aspartate receptor;    NMDAR;    siRNA;    Single cell calcium imaging;   

DOI  :  10.1186/s12964-019-0487-3

来源: DOAJ

【 摘 要 】

Abstract Background In vitro chondrogenesis depends on the concerted action of numerous signalling pathways, many of which are sensitive to the changes of intracellular Ca2+ concentration. N-methyl-D-aspartate (NMDA) glutamate receptor is a cation channel with high permeability for Ca2+. Whilst there is now accumulating evidence for the expression and function of NMDA receptors in non-neural tissues including mature cartilage and bone, the contribution of glutamate signalling to the regulation of chondrogenesis is yet to be elucidated. Methods We studied the role of glutamatergic signalling during the course of in vitro chondrogenesis in high density chondrifying cell cultures using single cell fluorescent calcium imaging, patch clamp, transient gene silencing, and western blotting. Results Here we show that key components of the glutamatergic signalling pathways are functional during in vitro chondrogenesis in a primary chicken chondrogenic model system. We also present the full glutamate receptor subunit mRNA and protein expression profile of these cultures. This is the first study to report that NMDA-mediated signalling may act as a key factor in embryonic limb bud-derived chondrogenic cultures as it evokes intracellular Ca2+ transients, which are abolished by the GluN2B subunit-specific inhibitor ifenprodil. The function of NMDARs is essential for chondrogenesis as their functional knock-down using either ifenprodil or GRIN1 siRNA temporarily blocks the differentiation of chondroprogenitor cells. Cartilage formation was fully restored with the re-expression of the GluN1 protein. Conclusions We propose a key role for NMDARs during the transition of chondroprogenitor cells to cartilage matrix-producing chondroblasts.

【 授权许可】

Unknown