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The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte

Abstract : The differentiated phenotype of chondrocyte is lost in pathological situations and after interleukin (IL)-1 challenge. Wnt proteins and the inorganic pyrophosphate (PP i) transporter Ank regulate the differentiation process in many cell types. We investigated the possible contribution of Ank and/or PP i to the maintenance of the differentiated chondrocyte phenotype with special care to Wnt signaling. Primary articular chondrocytes lost their phenotype upon IL-1 challenge, with cessation of type II collagen and Sox-9 expression. Ank expression and PP i transport were strongly reduced by IL-1, whereas Wnt-5a was the only Wnt protein increased. Transient overexpression of Ank counteracted most of IL-1 effects on Type II collagen, Sox-9, and Wnt-5a expression. When resting chondrocytes were transfected with a siRNA against Ank, this reproduced the phenotype induced by IL-1. In both cases, no markers for hypertrophic chondrocytes were detected. The conditioned supernatant from chondrocytes knocked-down for Ank contained Wnt-5a, which activated Tcf/Lef reporter plasmids and promoted translocation of-catenin into the nucleus without activating the c-Jun N-terminal kinase (JNK) pathway. Supple-mentation with PP i compensated for most effects of Ank deficiency on Type II collagen, Sox-9, and Wnt-5 expression, both in IL-1 and Ank knock-down conditions. Phenotype changes induced by IL-1 were also supported by activation of the JNK pathway, but this latter was not sensitive to PP i supplementa-tion. Altogether our data demonstrate that the transport of PP i by ANK contributed to the maintenance of the differentiated phenotype of chondrocyte by controlling the canonical Wnt pathway in a Wnt-5a-dependent manner.
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Contributor : Frédéric Cailotto <>
Submitted on : Thursday, February 15, 2018 - 1:05:36 PM
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Frederic Cailotto, Sylvie Sébillaud, Patrick Netter, Jean-Yves Jouzeau, Arnaud Bianchi. The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (14), pp.10572-10582. ⟨10.1074/jbc.M109.050534⟩. ⟨hal-01704435⟩



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