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

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 Y357 and LATS1-p-YAPS127. S127 . 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 down- regulate 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 Y357 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 Y357 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.