Abstract:
: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-β1 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-β1 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-β1 on ANK, PC-1 or PiT-1 mRNA (RT-qPCR) and protein (Western blot) levels. PC-1 activity was also increased by TGF-β1 and further potentiated by ePi supplementation. TNAP mRNA and activity became undetectable in response to TGF-β1. These data suggest that ePi could increase ePPi level by changing the control of ANK and PC-1 expression by TGF-β1, further highlighting an adaptative regulation of the Pi/PPi balance to prevent basic calcium phosphate deposition into the joints.
journal_name
Biomed Mater Engjournal_title
Bio-medical materials and engineeringauthors
Hamade T,Bianchi A,Sebillaud S,Netter P,Jouzeau JY,Cailotto Fdoi
10.3233/BME-2010-0634subject
Has Abstractpub_date
2010-01-01 00:00:00pages
209-15issue
3eissn
0959-2989issn
1878-3619pii
A042Q387706TT506journal_volume
20pub_type
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