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1篇 您的检索式：作者名="Valentin Estibals"

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		题名	作者	年代	出处	被引量
	1	Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia显示文摘A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.	Ludovic Martin Nabil Kaci Catherine Benoist-Lasselin Marine Mondoloni Suzanne Decaudaveine Valentin Estibals Maxence Cornille Léa Loisay Justine Flipo Benoît Demuynck Maria de la Luz Cádiz-Gurrea Florent Barbault Salvador Fernández-Arroyo Laurent Schibler Antonio Segura-Carretero Emilie Dambroise Laurence Legeai-Mallet	2022	Bone Research2022，10，1：	1

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