Inorganic phosphate (Pi) modulates the expression of key regulatory proteins of the inorganic pyrophosphate (PPi) metabolism in TGF-beta1-stimulated chondrocytes.
Fiche publication
Date publication
janvier 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr JOUZEAU Jean-Yves
Tous les auteurs :
Hamade T, Bianchi A, Sebillaud S, Netter P, Jouzeau JY, Cailotto F
Lien Pubmed
Résumé
The balance between extracellular inorganic phosphate (ePi) and extracellular inorganic pyrophosphate (ePPi) is controlled by four membrane proteins: the transporters ANK (exporting PPi outside the cells) and PiT-1 (importing ePi into the cells), and the enzymes PC-1 (generating ePPi from nucleotides) and Tissue Non-specific Alkaline Phosphatase (TNAP, hydrolyzing ePPi into ePi). TGF-beta1 was shown to stimulate ANK and PC-1 expression in articular chondrocytes, and subsequent ePPi level, as well as to increase ePi uptake by inducing PiT-1 expression in a chondrogenic cell line. Thus, we investigated the ability of ePi to modulate the effect of TGF-beta1 on the regulatory proteins of the ePi/ePPi balance in chondrocytes. In the pathophysiological range of 0.01-1 mM, ePi was inactive by itself but potentiated the stimulatory effects of TGF-beta1 on ANK, PC-1 or PiT-1 mRNA (RT-qPCR) and protein (Western blot) levels. PC-1 activity was also increased by TGF-beta1 and further potentiated by ePi supplementation. TNAP mRNA and activity became undetectable in response to TGF-beta1. These data suggest that ePi could increase ePPi level by changing the control of ANK and PC-1 expression by TGF-beta1, further highlighting an adaptative regulation of the Pi/PPi balance to prevent basic calcium phosphate deposition into the joints.
Référence
Biomed Mater Eng. 2010 Jan 1;20(3):209-15.