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Eur J Cell Biol. 2018 Nov;97(8):533-545. doi: 10.1016/j.ejcb.2018.09.003. Epub 2018 Sep 24.

Anti-osteoclastic effects of C-glucosidic ellagitannins mediated by actin perturbation.

Author information

1
Institut de Génomique Fonctionnelle de Lyon, (ENS-UMR 5242), Université de Lyon, F-69007, Lyon Cedex, France.
2
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.
3
Institute for Integrative Biology of the Cell, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, F-91198, Gif-sur-Yvette Cedex, France.
4
Inserm U1026, University of Bordeaux, Tissue Bioengineering, U1026, F-33076 Bordeaux, France.
5
Centre de Recherche Cardio-Thoracique de Bordeaux (INSERM U1045), Université de Bordeaux, F-33076, Bordeaux Cedex, France.
6
European Institute of Chemistry and Biology, (UMS 3033/US 001), Université de Bordeaux, 33607 Pessac Cedex, F-33607, France.
7
Institut des Sciences Moléculaires (CNRS-UMR 5255), Université de Bordeaux, Talence Cedex, F-33405, France.
8
Institut des Sciences Moléculaires (CNRS-UMR 5255), Université de Bordeaux, Talence Cedex, F-33405, France. Electronic address: stephane.quideau@u-bordeaux.fr.
9
Centre de Recherche Cardio-Thoracique de Bordeaux (INSERM U1045), Université de Bordeaux, F-33076, Bordeaux Cedex, France. Electronic address: elisabeth.genot@inserm.fr.

Abstract

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.

KEYWORDS:

Actin dynamics; Cytoskeleton; Medicinal biology; Osteoclast biology; Podosomes; Polyphenol sciences

PMID:
30287085
DOI:
10.1016/j.ejcb.2018.09.003
[Indexed for MEDLINE]

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