Molecular mechanism of FZD2 in alleviating osteoporosis by stabilizing estrogen receptor alpha via activating β-catenin
CUI Yongjian
LI Yan
WANG Guizhi
Abstract：Objective To evaluate and explore the efficacy and mechanisms of Frizzled 2(FZD2)on increasing bone mass of mice with bilateral ovariectomy(OVX).Methods A mouse model of OVX-induced osteoporosis was established.Adenovirus overexpressing(OE)FZD2 was constructed.Thirty female C57BL/6J mice aged 6-8 weeks were randomly assigned into the Control group,Sham group,OVX Model group,OVX Model+E2 Treatment group(OVX+treatment of estradiol[E2]),OVX Model+FZD2 Treatment-L group(OVX+injection of adenovirus OE FZD2 into the mouse left hind knee joint)and OVX Model+Control-R group(OVX+injection of control vector into the mouse left hind knee joint),with 6 mice per group.Microcomputed tomography(Micro-CT)was used to measure the bone mass of tibial trabecular and cortical bone in the left and right hind limbs of mice.Expression levels of FZD2,active-β-catenin,β-catenin,phosphorylated-estrogen receptor alpha(p-ERα),ERα,Runt-related transcription factor 2(Runx2)and alkaline phosphatase(ALP)in the mouse tibia were determined by Western blot.The direct interaction of ERα and β-catenin in mouse embryonic osteoblasts MC3T3-E1 treated with Wnt3a,E2 and adenovirus-OE-FZD2 was determined by co-immunoprecipination(co-IP).Results Compared with those of OVX Model group,FZD2,active-β-catenin,β-catenin,p-ERα,ERα,Runx2 and ALP in mouse bone tissue of OVX Model+E2 Treatment group were significantly up-regulated(P＜0.05).Trabecular bone volume fraction(BV/TV％)and trabecular number(Tb.N)were significantly higher in the OVX Model+E2 Treatment group than those of OVX Model group(P＜0.05).Trabecular separation(Tb.Sp)and cortical bone marrow area(Ma.Ar)were significantly lower in the OVX Model+E2 Treatment group than those of OVX Model group(P＜0.05).Compared with OVX Model+E2 Treatment group,OVX Model+FZD2 Treatment-L group achieved similar efficacy as that in the OVX Model+E2 Treatment group(P＞0.05).After the MC3T3-E1 cells were treated with Wnt3a or E2 or adenovirus-OE-FZD2,co-IP and Western blot results showed that ERα and β-catenin were positive in all three treatment groups.Conclusion Over-expression and activation of FZD2 alleviates osteoporosis by stabilizing estrogen receptor alpha via the activated β-catenin.
Keywords：osteoporosisestrogenestrogen receptorWnt/β-catenin signalingFZD2
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 201-206 )