Abstract： Objective To investigate the molecular mechanisms by which silencing of the Periostin gene affects the expression of Runx2,receptor activator of nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in murine osteoblasts and its impact on bone resorption activity.Methods Murine osteoblast cell line MC3T3-E1 was di-vided into an experimental group and a control group.The experimental group was transfected with LVpFU-GW-016PSC66473-1 virus,while the control group received pFU-GW-016PSC53349-1 virus to ensure equivalent cellu-lar conditions.The efficiency of gene silencing was assessed using MDC method,and the protein expression of Runx2,RANKL,and OPG in both groups was evaluated by Western blotting.Results Following Periostin silencing,the experi-mental group showed significantly enhanced fluorescence expression compared to the control group(P＜0.01).Protein expression of Runx2 and RANKL was significantly decreased(P＜0.05),whereas OPG expression was markedly in-creased(P＜0.05)in the experimental group compared to the control group.Conclusion Silencing of Periostin alters RANKL and OPG expression in murine osteoblasts,potentially influencing the Runx2 gene via the nuclear factor-kappa B(NF-κB)signaling pathway.This enhancement of osteoblast function may contribute to the inhibition of bone resorp-tion.