Mechano-growth factor regulates periodontal ligament stem cell proliferation and differentiation through Fyn-RhoA-YAP signaling

Biochem Biophys Res Commun. 2024 Nov 12:733:150450. doi: 10.1016/j.bbrc.2024.150450. Epub 2024 Jul 25.

Abstract

Background: Mechano-growth factor (MGF), which is a growth factor produced specifically in response to mechanical stimuli, with potential of tissue repair and regeneration. Our previous research has shown that MGF plays a crucial role in repair of damaged periodontal ligaments by promoting differentiation of periodontal ligament stem cells (PDLSCs). However, the molecular mechanism is not fully understood. This study aimed to investigated the regulatory effect of MGF on differentiation of PDLSCs and its molecular mechanism.

Methods: Initially, we investigated how MGF impacts cell growth and differentiation, and the relationship with the activation of Fyn-p-YAPY357 and LATS1-p-YAPS127. Then, inhibitors were used to interfere Fyn phosphorylation to verify the role of Fyn-p-YAP Y357 signal after MGF stimulation; moreover, siRNA was used to downregulate YAP expression to clarify the function of YAP in PDLSCs proliferation and differentiation. Finally, after C3 was used to inhibit the RhoA expression, we explored the role of RhoA in the Fyn-p-YAP Y357 signaling pathway in PDLSCs proliferation and differentiation.

Results: Our study revealed that MGF plays a regulatory role in promoting PDLSCs proliferation and fibrogenic differentiation by inducing Fyn-YAPY357 phosphorylation but not LATS1-YAP S127 phosphorylation. Moreover, the results indicated that Fyn could not activate YAP directly but rather activated YAP through RhoA in response to MGF stimulation.

Conclusion: The research findings indicated that the Fyn-RhoA-p-YAPY357 pathway is significant in facilitating the proliferation and fibrogenic differentiation of PDLSCs by MGF. Providing new ideas for the study of MGF in promoting periodontal regenerative repair.

Keywords: Mechano-growth factor (MGF); Periodontal ligament stem cells (PDLSCs); RhoA; Yes-associated protein (YAP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Cell Differentiation* / drug effects
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Periodontal Ligament* / cytology
  • Periodontal Ligament* / metabolism
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-fyn* / genetics
  • Proto-Oncogene Proteins c-fyn* / metabolism
  • Signal Transduction*
  • Stem Cells* / cytology
  • Stem Cells* / drug effects
  • Stem Cells* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins* / metabolism
  • rhoA GTP-Binding Protein* / metabolism

Substances

  • Proto-Oncogene Proteins c-fyn
  • rhoA GTP-Binding Protein
  • YAP-Signaling Proteins
  • Adaptor Proteins, Signal Transducing
  • FYN protein, human
  • Transcription Factors
  • mechano-growth factor E, human
  • YAP1 protein, human
  • RHOA protein, human
  • Insulin-Like Growth Factor I
  • LATS1 protein, human
  • Protein Serine-Threonine Kinases