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

Wei, Q. et al. (2020) BMP‐2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ. Advanced Science, 7(15), 1902931. (doi: 10.1002/advs.201902931) (PMID:32775147) (PMCID:PMC7404154)

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.

• Item Type: Articles
• Additional Information: The work was supported by Deutsche Forschungsgemeinschaft Sonderforschungsbereich (German Science Foundation Collaborative Research Center) DFG SFB TRR79 TP M09 and TP B05. The support of the Max Planck Society is greatly acknowledged. Q.W. also acknowledges the financial support from National Natural Science Foundation of China (grant no. 51973129) and State Key Laboratory of Polymer Materials Engineering, Sichuan University (grant no. sklpme2018-3-09).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Inman, Professor Gareth
• Authors: Wei, Q., Holle, A., Liu, J., Posa, F., Biagioni, F., Croci, O., Benk, A. S., Young, J., Noureddine, F., Deng, J., Zhang, M., Inman, G. J., Spatz, J. P., Campaner, S., and Cavalcanti‐Adam, E. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Advanced Science
• Publisher: Wiley
• ISSN: 2198-3844
• ISSN (Online): 2198-3844
• Published Online: 16 June 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Advanced Science 7(15):1902931
• Publisher Policy: Reproduced under a Creative Commons license