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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 Connect in order to contact the contributor
Submitted on : Thursday, February 15, 2018 - 1:05:36 PM
Last modification on : Friday, October 15, 2021 - 4:48:02 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, 2010, 285 (14), pp.10572-10582. ⟨10.1074/jbc.M109.050534⟩. ⟨hal-01704435⟩



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