Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line.

Adaptor Proteins, Signal Transducing / metabolism Animals Cell Culture Techniques, Three Dimensional Chemokines / metabolism HEK293 Cells Humans Mechanotransduction, Cellular Mice Osteocytes / physiology Stress, Mechanical YAP-Signaling Proteins / metabolism

Journal

Laboratory investigation; a journal of technical methods and pathology
ISSN: 1530-0307
Titre abrégé: Lab Invest
Pays: United States
ID NLM: 0376617

Informations de publication

Date de publication:
12 2021
Historique:
received: 27 02 2021
accepted: 19 08 2021
revised: 17 08 2021
pubmed: 16 9 2021
medline: 30 12 2021
entrez: 15 9 2021
Statut: ppublish

Résumé

Osteocytes are mechanosensitive cells that control bone remodeling in response to mechanical loading. To date, specific signaling pathways modulated by mechanical loading in osteocytes are not well understood. Yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the main effectors of the Hippo pathway, are reported to play a role in mechanotransduction and during osteoblastogenesis. Here, we hypothesized that YAP/TAZ signaling mediates osteocyte mechanosensing to target genes of the bone remodeling process. We aimed to investigate the contribution of YAP/TAZ in modulating the gene expression in an osteocyte-like cell line MLO-Y4. We developed a 3D osteocyte compression culture model from an MLO-Y4 osteocyte cell line embedded in concentrated collagen hydrogel. 3D-mechanical loading led to the increased expression of mechanosensitive genes and a subset of chemokines, including M-csf, Cxcl1, Cxcl2, Cxcl3, Cxcl9, and Cxcl10. The transcription regulators YAP and TAZ translocated to the nucleus and upregulated their target genes and proteins. RNAseq analysis revealed that YAP/TAZ knockdown mediated the regulation of several genes including osteocyte dendrite formation. Use of YAP/TAZ knockdown partially blunted the increase in M-csf and Cxcl3 levels in response to MLO-Y4 compression. These findings demonstrate that YAP/TAZ signaling is required for osteocyte-like cell mechano-transduction, regulates the gene expression profiles and controls chemokine expression.

Identifiants

DOI: 10.1038/s41374-021-00668-5 PMID: 34521992
pubmed: 34521992
doi: 10.1038/s41374-021-00668-5
pii: S0023-6837(22)00387-7
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Chemokines 0
Wwtr1 protein, mouse 0
YAP-Signaling Proteins 0
Yap1 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1597-1604

Informations de copyright

© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.

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Auteurs

Mylene Zarka (M)

INSERM UMR 1132, Biologie de l'os et du cartilage (BIOSCAR), Hôpital Lariboisière, Paris, France.
Université de Paris, Faculté de Santé, UFR de médecine, Paris, France.

Francois Etienne (F)

Université de Paris, Faculté des Sciences, UFR Sciences Fondamentales et Biomédicales, Paris, France.
INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs (T3S), Campus Saint-Germain-des-Prés, Paris, France.
BioMedTech Facilities - INSERM US 36 | CNRS UMS 2009 | Université de Paris. Faculté des Sciences, UFR Sciences Fondamentales et Biomédicales, Paris, France.

Morgane Bourmaud (M)

INSERM UMR 1132, Biologie de l'os et du cartilage (BIOSCAR), Hôpital Lariboisière, Paris, France.
Université de Paris, Faculté de Santé, UFR de médecine, Paris, France.

Denis Szondi (D)

School of Biological Sciences, University of Manchester, Manchester, UK.

Jean-Marc Schwartz (JM)

School of Biological Sciences, University of Manchester, Manchester, UK.

Kristine Kampmann (K)

Eurofins GATC Biotech GmbH, Konstanz, Allemagne.

Christophe Helary (C)

Sorbonne Université, CNRS, Laboratoire de la Chimie de la Matière Condensée (LCMCP), Paris, France.

Francois Rannou (F)

Université de Paris, Faculté de Santé, UFR de médecine, Paris, France.
INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs (T3S), Campus Saint-Germain-des-Prés, Paris, France.
BioMedTech Facilities - INSERM US 36 | CNRS UMS 2009 | Université de Paris. Faculté des Sciences, UFR Sciences Fondamentales et Biomédicales, Paris, France.
AP-HP. Centre Université de Paris, Service de Rééducation et de Réadaptation de l'Appareil locomoteur et des Pathologies du Rachis, Hôpital Cochin, Paris, France.

Eric Haÿ (E)

INSERM UMR 1132, Biologie de l'os et du cartilage (BIOSCAR), Hôpital Lariboisière, Paris, France.
Université de Paris, Faculté de Santé, UFR de médecine, Paris, France.

Martine Cohen-Solal (M)

INSERM UMR 1132, Biologie de l'os et du cartilage (BIOSCAR), Hôpital Lariboisière, Paris, France. martine.cohen-solal@inserm.fr.
Université de Paris, Faculté de Santé, UFR de médecine, Paris, France. martine.cohen-solal@inserm.fr.
ORCID: 0000-0002-8582-8258

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Eucaryotes › Animaux › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Techniques de cultures cellulaires tridimensionnelles › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Chimiokines › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mécanotransduction cellulaire › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Ostéoblastes › Ostéocytes › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Phénomènes physiques › Phénomènes mécaniques › Contrainte mécanique › Mechanical loading activates the YAP/TAZ...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Mechanical loading activates the YAP/TAZ...