Institut de Génomique Fonctionnelle de Lyon, (ENS-UMR 5242), Université de Lyon, F-69007, Lyon Cedex, France.
Centre de Recherche Cardio-Thoracique de Bordeaux (INSERM U1045), Université de Bordeaux, F-33076, Bordeaux Cedex, France; Department of Chemistry and Biotechnology, Division of Gene Technology, Tallinn University of Technology, 12618, Tallinn, Estonia.
Eur J Cell Biol. 2018 Nov;97(8):533-545. doi: 10.1016/j.ejcb.2018.09.003. Epub 2018 Sep 24.
Actin subunits assemble into actin filaments whose dynamics and three-dimensional architectures are further regulated by a variety of cellular factors to establish the functional actin cytoskeleton. The C-glucosidic ellagitannin vescalagin and its simpler analogue vescalin, affect both the dynamics and the ultrastructure of the actin cytoskeleton by directly binding to F-actin. Herein, we show that in vitro, the two compounds induce the formation of distinct F-actin networks characterized by different superstructures and dynamics. In living mature osteoclasts, highly specialized bone-degrading cells that constantly remodel their cytoskeleton, vescalagin and vescalin alter actin dynamics at podosomes and compromise the integrity of the podosome belt that forms the bone-degrading apparatus. Both compounds target the bone-resorbing activity at concentrations that preserve osteoclastic maturation and survival and with no detectable impact on the behaviour of bone-forming osteoblastic cells. This anti-osteoclastic activity of vescalagin and vescalin reveals the potential of targeting actin dynamics as a new therapeutic opportunity and, in this case, as a plausible approach for the local treatment of osteoporosis.
肌动蛋白亚基组装成肌动蛋白丝，其动态和三维结构进一步受到各种细胞因子的调节，以建立功能性的肌动蛋白细胞骨架。C-糖苷型鞣花单宁酸及其简单类似物鞣花酸通过直接结合 F-肌动蛋白来影响肌动蛋白细胞骨架的动态和超微结构。本文中，我们表明，在体外，这两种化合物诱导形成具有不同超结构和动力学特征的独特 F-肌动蛋白网络。在成熟的破骨细胞中，破骨细胞是高度特化的骨降解细胞，它们不断重塑其细胞骨架，鞣花酸和鞣花酸会改变破骨细胞足突处的肌动蛋白动力学，并损害形成骨降解装置的足突带的完整性。这两种化合物以在保持破骨细胞成熟和存活的浓度靶向骨吸收活性，并且对成骨细胞的行为没有可检测到的影响。鞣花酸和鞣花酸的这种抗破骨细胞活性表明，靶向肌动蛋白动力学具有作为一种新的治疗机会的潜力，在这种情况下，作为骨质疏松症局部治疗的合理方法。
