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  BMP‐2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ

Wei, Q., Holle, A. W., Li, J., Posa, F., Biagioni, F., Croci, O., et al. (2020). BMP‐2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ. Advanced Science, e-pip(1902931), 1-15. doi:10.1002/advs.201902931.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-9552-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-D741-E
Genre: Journal Article

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 Creators:
Wei, Qiang1, 2, Author              
Holle, Andrew W.1, 2, Author              
Li, Jie1, Author              
Posa, Francesca2, 3, Author              
Biagioni, Francesca, Author
Croci, Ottavio, Author
Benk, Amelie S.1, Author              
Young, Jennifer L.1, 2, Author              
Noureddine, Fatima3, Author              
Deng , Jie, Author
Zhang, Man3, Author              
Inman, Gareth J., Author
Spatz, Joachim P.1, 2, Author              
Campaner, Stefano, Author
Cavalcanti-Adam, Elisabetta Ada1, 2, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              
3Max Planck Institute for Medical Research, Max Planck Society, ou_1125545              

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Free keywords: BMP‐2, cell differentiation, mechanotransduction, signaling, YAP/TAZ
 Abstract: Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP‐2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP‐2 pathway‐associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP‐2 removal, suggesting that they act as a “molecular memory unit.” Thus, synergistic stimulation with BMP‐2 and mechanical cues drives osteogenic differentiation in a programmable fashion.

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Language(s): eng - English
 Dates: 2020-02-282019-10-182020-03-302020-06-16
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/advs.201902931
 Degree: -

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Title: Advanced Science
  Other : Adv. Sci.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: e-pip (1902931) Sequence Number: - Start / End Page: 1 - 15 Identifier: Other: 2198-3844
CoNE: https://pure.mpg.de/cone/journals/resource/2198-3844