Differential Impact of Fluid Shear Stress and YAP/TAZ on BMP/TGF-β Induced Osteogenic Target Genes.

BMP signaling TAZ YAP fluid shear stress osteogenic differentiation

Journal

Advanced biology
ISSN: 2701-0198
Titre abrégé: Adv Biol (Weinh)
Pays: Germany
ID NLM: 101775319

Informations de publication

Date de publication:
Feb 2021
Historique:
revised: 08 12 2020
received: 17 02 2020
entrez: 8 9 2022
pubmed: 1 2 2021
medline: 1 2 2021
Statut: ppublish

Résumé

Bone is a remarkable dynamic structure, which integrates mechanical and biochemical signaling inputs. Interstitial fluid in the intramedullary space transmits signals derived from compression-induced fluid shear stress (FSS) to stimulate osteoblasts for bone formation. Using a flow system and human osteoblasts, this study demonstrates how BMP/TGF-β  signaling integrates stimuli derived from FSS and YAP/TAZ and confirms these findings by transcriptome analyses. Here, FSS positively affects the phosphorylation of both SMAD1/5 and SMAD2/3, the respective BMP- and TGFβ-R-SMADs. Increase in phosphorylated SMAD1/5 levels affects distinct target genes, which are susceptible to low levels of phosphorylated SMADs (such as ID1-3) or dependent on high levels of phosphorylated SMAD1/5 (NOG, noggin). Thus, FSS lowers the threshold for genes dependent on high levels of phosphorylated SMAD1/5 when less BMP is available. While the impact of FSS on direct BMP target genes is independent of YAP/TAZ, FSS acts cooperatively with YAP/TAZ on TGF-β  target genes, which are shared by both pathways (such as CTGF). As mechanical stimuli are key in bone regeneration, their crosstalk to biochemical signaling pathways such as BMP and TGF-β and YAP/TAZ acts on different levels, which allows now to think about new and more specified intervention strategies for age-related bone loss.

Identifiants

pubmed: 36073990
doi: 10.1002/adbi.202000051
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2000051

Subventions

Organisme : Max-Planck IMPRS- Biology and Computation
Organisme : Deutsche Forschungsgemeinschaft
ID : GSC 203
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2165
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB958

Informations de copyright

© 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH.

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Auteurs

Maria Reichenbach (M)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.

Paul-Lennard Mendez (PL)

International Max Planck Research School for Biology and Computation, Max Planck Institute for Molecular Genetics, Ihnestr. 63, Berlin, 14195, Germany.

Carolina da Silva Madaleno (C)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité-Universitätsmedizin Berlin, Föhrer Str. 15, Berlin, 13353, Germany.

Vladimir Ugorets (V)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.

Paul Rikeit (P)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité-Universitätsmedizin Berlin, Föhrer Str. 15, Berlin, 13353, Germany.

Stefan Boerno (S)

Sequencing Core Facility, Max Planck Institute for Molecular Genetics, Ihnestr. 63, Berlin, 14195, Germany.

Jerome Jatzlau (J)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité-Universitätsmedizin Berlin, Föhrer Str. 15, Berlin, 13353, Germany.

Petra Knaus (P)

Institute of Chemistry/Biochemistry, Freie Universität Berlin, Thielallee 63, Berlin, 14195, Germany.

Classifications MeSH