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Journal Article

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

MPS-Authors
/persons/resource/persons173872

Wei,  Qiang
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

/persons/resource/persons189311

Holle,  Andrew W.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

/persons/resource/persons232994

Li,  Jie
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons217907

Posa,  Francesca
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;
Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons227179

Benk,  Amelie S.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons189321

Young,  Jennifer L.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

/persons/resource/persons248393

Noureddine,  Fatima
Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons248395

Zhang,  Man
Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons76135

Spatz,  Joachim P.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

/persons/resource/persons75354

Cavalcanti-Adam,  Elisabetta Ada
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201902931
(Any fulltext)

https://doi.org/10.1002/advs.201902931
(Any fulltext)

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Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0006-9552-5
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.