Mechanism of Baicalein Regulating OPG/RANKL Signaling Pathway to Intervene Bone Mineral Density and Ferroptosis in Osteoporosis Rats Model
LI Jikai
CHEN Xiugai
LI Tongxian
WU Huarong
Abstract：Objective To investigate the interventional mechanism of Baicalein intervening osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)signaling pathway on bone mineral density and ferroptosis in osteoporosis(OP)rats model.Methods A total of 60 SD rats were randomly divided into blank group,model group,control group and experimental group,with 15 rats in each.The blank group was not treated,while the other 3 groups of rats were used to establish ovariectomized OP model.Af-ter successful modeling,the experimental group was given 20 mg/(kg·d)Baicalein by gavage,the control group was given alendronate sodium and vitamin D3[6.25 mg/(kg·d)]by gavage,the rats in the blank group and the model group were given normal saline[10 ml/(kg·d)]by gavage for 12 con-secutive weeks.The changes in bone mineral density of the tibia and distal femur of rats in each group were detected;the levels of changes of glutathione(GSH),reactive oxygen species(ROS)and malondialdehyde(MDA)in rat serum were detected by enzyme-linked immunosorbent assay(ELISA);computed tomography(CT)was used to analyze trabecular bone microstructural index bone volume fraction(BV/TV),trabecular connectivity density(Conn.D),trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp)and structure model index(SMI)in lumbar spine(L1-3)of rats in each group;the protein expression of ferroptosis central regulator glutathione peroxidase 4(GPX4)in femoral tissue of rats in each group was detected by immunohistochemistry;the mRNA expressions of OPG,Runt-related transcription factor 2(Runx2)and RANKL in OPG/RANKL signaling pathway in each group were detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with the blank group,the bone mineral density of tibia and distal femur in the model group decreased significantly,and the microstructural indexes of lumbar spine trabecu-lar bone were significantly changed(all P＜0.05),serum ferroptosis-related index GSH decreased(P＜0.05),the con-tents of ROS and MDA increased(all P＜0.05),and the expression of GPX4 protein in femoral tissue decreased(P＜0.05),the mRNA expressions of OPG and Runx2 in OPG/RANKL signaling pathway significantly decreased(all P＜0.05),the mRNA expression of RANKL significantly increased(P＜0.05).Compared with the model group,the bone mineral density of tibia and distal femur in the control group and the experimental group significantly increased(all P＜0.05),trabecular bone microstructural index were significantly improved(P＜0.05),the GSH ferroptosis-related index increased(P＜0.05),the contents of ROS and MDA decreased(all P＜0.05),the expression of GPX4 protein in femoral tissue increased(P＜0.05),the mRNA expressions of OPG and Runx2 in OPG/RANKL signaling pathway significantly increased(all P＜0.05),RANKL mRNA expression significantly decreased(P＜0.05).Conclusion Baicalein can im-prove bone mineral density,repair microstructure of trabecular bone and affect the key factors and protein expressions of ferroptosis in OP rats,its mechanism may be related to Baicalein regulating OPG/RANKL signaling pathway.
Keywords：FerroptosisOsteoporosisBaicaleinOsteoprotegerin/receptor activator of NF-κB ligandBone min-eral density
Publication Date：2023-12-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 993-997 )