Platelet-derived growth factor-BB inhibits MC3T3-E1 cell senescence and promotes osteogenic differentiation by regulating the AKT signaling pathway
WANG Fan
LIU Xinyi
XU Chenyang
Abstract：Objective To establish an in vitro senescence model in mouse embryonic osteoblast precursor cells(MC3T3-E1)and to investigate the effects of platelet-derived growth factor-BB(PDGF-BB)on senescence and osteogenic differentiation of MC3T3-E1 cells,and the potential mechanisms by detecting cell senescence and osteogenic differentiation related indicators.Methods MC3T3-E1 cells were induced with H2O2 to create the in vitro senescence model,followed by PDGF-BB intervention.Cell senescence markers were assessed,including cell proliferation,senescence-associated β-galactosidase(SA-β-gal)staining-positive cells,reactive oxygen species(ROS)generation,mRNA expressions of cyclin-dependent kinase inhibitors 2A(P16)and 1A(P21),as well as inflammatory factors interleukin-6(IL-6)and interleukin-8(IL-8),and osteogenic differentiation markers.The protein kinase B(AKT)signaling pathway was explored using the inhibitor MK-2206.Results Compared to the Control group,the H2O2 group exhibited decreased cell proliferation,increased SA-β-gal-positive cells,elevated ROS generation,and up-regulated P16,P21,IL-6,and IL-8(P＜0.05),as well as impaired osteogenic differentiation ability(P＜0.05).The H2O2+PDGF-BB group showed significantly higher cell proliferation and osteogenic differentiation capacity than the H2O2 group(P＜0.05),but less number of SA-β-gal-positive cells,and lower ROS production,and expression levels of P16,P21,IL-6,and IL-8(P＜0.05).In contrast,the H2O2+PDGF-BB+MK-2206 group demonstrated significantly lower cell proliferation and osteogenic differentiation ability compared to the H2O2+PDGF-BB group(P＜0.05),but higher SA-β-gal-positive cells,ROS generation,and expression levels of P16,IL-6,and IL-8(P＜0.05).Conclusion PDGF-BB can counteract cell senescence in murine MC3T3-E1 cells and promote osteogenic differentiation of senescent cells by reactivating the AKT signaling pathway.
Keywords：cell senescencePDGF-BBosteogenic differentiationAKT signaling pathway
Publication Date：2025-11-26
Online Publishing Date：2025-12-12(First online date of this platform, not the publication date of the document)
Pages：6( 1765-1770 )