Explore the Mechanism of Action of Psoralen on Bone Protection in Postmenopausal Osteoporosis Rats Based on the Wnt Sig-naling Pathway
HE Tiantian
TANG Fang
YE Haixia
ZHAO Chaoyue
WANG Shasha
LIU Huan
Abstract：Objective To explore the mechanism of the osteoprotective effect of psoralen on postmenopausal osteoporosis(PMOP)rats by regulating wingless type MMTV integration site family(Wnt)signaling pathway.Methods A total of 60 SPF grade female SD rats were randomly divided into blank group,model group,estradiol tablet group(0.09 mg/kg,once a day)and low-dose psoralen,medi-um-dose psoralen,high-dose psoralen groups(11,22,44 mg/kg,3 times a day),with 10 rats in each.Except for the blank group,the PMOP rat models were estab-lished in the remaining groups by ovariectomy.After 6 weeks of drug intervention,the rats were anesthetized and the samples were collected,the bone mineral density of the femur was measured;the pathological morphology of the fem-oral tissues was observed by hematoxylin-eosin(HE)staining;the mRNA expressions of dickkopf-related protein 1(DKK1),β-catenin and runt-related transcription factor 2(Runx2)in the femoral tissues of rats were detected by reverse transcription polymerase chain reaction(RT-PCR).Results ① In terms of femoral bone mineral density,compared with the blank group,the bilateral femoral bone mineral density of rats in the model group significantly decreased(all P＜0.05);compared with the model group,the bilateral femoral bone mineral density of rats in estradiol tablet group and high-dose psoralen group as well as left femoral bone mineral density of rats in low-dose psoralen group and middle-dose psoralen group significantly increased(all P＜0.05);compared with the estradiol tablet group,the bilateral femoral bone mineral density of rats in low-dose psoralen group was lower(P＜0.05).② In terms of the pathological morphology of femoral tissues,compared with the blank group,the trabecular bone structures of rats in model group was significantly damaged and arranged disorderly,with an increase in bone resorption pores,showing obvious characteristics of osteoporo-sis;compared with the model group,the trabecular bone structures of rats in estradiol tablet group,low-dose psoralen group,medium-dose psoralen group and high-dose psoralen group were improved,among which,the continuity of trabec-ular bone in the estradiol tablet group and the high-dose psoralen group significantly increased,the bone lacunae were re-duced,and the bone resorption pores decreased.③ In terms of mRNA expression,compared with the blank group,the expression level of DKK1 mRNA in the femoral tissues of rats in the model group significantly increased,while the ex-pression levels of β-catenin and Runx2 mRNA significantly decreased(all P＜0.05);compared with the model group,the expression levels of DKK1 mRNA in the femoral tissues of rats in estradiol tablet group,medium-dose psoralen and high-dose psoralen group significantly decreased(P＜0.05),while the expression levels of β-catenin and Runx2 mRNA signifi-cantly increased(all P＜0.05);compared with the estradiol tablet group,the expression levels of β-catenin and Runx2 mRNA decreased in low-dose psoralen group(all P＜0.05),there were no statistically significant differences in the ex-pression levels of DKK1,β-catenin and Runx2 mRNA in the femoral tissues of rats in medium-dose psoralen and high-dose psoralen group(all P＞0.05).Conclusion Psoralen may exert an osteoprotective effect on PMOP rats ultimately by inhibiting the expression of DKK1,thereby activating the Wnt/β-catenin signaling pathway,upregulating the level of Runx2 and enhancing bone formation.
Keywords：Dickkopf-related protein 1PsoralenWingless type MMTV integration site family/β-catenin signaling pathwayPostmenopausal osteoporosisBone protection
Publication Date：2025-03-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 194-198 )