Study On The Correlation Between Postmenopausal Osteoporosis And Wnt/β-catenin-CEACAM1 Signaling Pathway And The Therapeutic Effect Of Gufang Qing’e Pills

Part one Serum carcinoembryonic antigen-related cell adhesion molecule 1 level in postmenopausal women:correlation with β-catenin and bone mineral densityObjective:The aim of this study is to assess the serum level of CEACAM1 in postmenopausal women and its correlation with β-catenin and bone mineral density(BMD).Methods:The BMD was measured at the lumbar spine(L1-L4)or the femoral neck using dual-energy X-ray absorptiometry(DXA).Serum CEACAM1,β-catenin,receptor activator of nuclear factor kappa-B(RANKL),osteoprotegerin(OPG),β-isomerized C-terminal crosslinking of type Ⅰ collagen(β-CTX),intact N-terminal propeptide of type Ⅰ collagen(PINP),estradiol and insulin were measured in 350 postmenopausal women.Patients were divided according to lumbar spine or femur neck T-scores into osteoporosis(group Ⅰ),osteopenia(group Ⅱ),and normal bone mineral density,the latter serving as control.Results:Serum CEACAM1 levels were significantly lower in group Ⅰ and Ⅱcompared to those in control subjects(P<0.05).Serum CEACAM1 levels correlated positively with β-catenin and BMD,but correlated negatively to the ratio between RANKL and OPG.Conclusions:This study provides evidence that decreased serum CEACAM1 levels are related to low BMD in postmenopausal women,and that serum CEACAM1 levels correlated positively to β-catenin.It suggests that CEACAM1 might influence the canonical Wnt/β-catenin pathway to modulate bone metabolism.Part two The effect of Qing’e Pill on serum CEACAM1 and β-catenin levels and bone mineral density in patients with postmenopausal osteoporosisObjective:To observe the effect of Chinese herbal Qing’E Pill on serum carcinoembryonic antigen related cell adhesion molecule 1(CEACAM1),beta chain protein(β-catenin)and bone mineral density(BMD)in patients with postmenopausal osteoporosis.Methods:80 cases of postmenopausal osteoporosis were randomly divided into Qing’e pill treatment group and control group,treatment for 6 months.Respectively,before treatment and after June were detected in the serum of CEACAM1 and[β-catenin level,dual energy X-ray absorptiometry(DEXA)determination of lumbar spine,femoral neck,trochanter and Ward’s triangle BMD.Results:Qing’e pill treatment group,serum CEACAM1 and P-catenin levels increased significantly(P<0.01)and placebo control group of CEACAM1 and(3-catenin levels did not change significantly.Qing’e pill treatment group than before treatment BMD had no obvious change(P>0.05),BMD in the placebo group was significantly lower treatment(P<0.01).Conclusion:Qing’e pill can improve postmenopausal osteoporosis patients’ serum CEACAM1 and β-catenin levels,and can effectively maintain the bone density in postmenopausal osteoporosis patients.Part three Evaluation of Qing’e Pill by Wnt/β-catenin Signaling Pathway in Bone Formation by Micro-CTObjective:To investigate the impact of Qing’e Pill(QEP)on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.Methods:Ninety-six 8-week-old specific pathogen free C57BL/6 mice were randomly divided into 4 groups(24/group):sham,ovariectomised osteoporosis model,oestradiol-treated,and QEP-treated groups.Three months after surgery,the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography(micro-CT)to acquire three-dimensional(3D)parameters of their cancellous bone microstructure.The impact of ovariectomy,the effect of oestradiol and QEP intervention on cancellous bone microstructure,and the expression of β-catenin were evaluated.Results:The oestradiol-and the QEP-treated groups exhibited a significant increase in the bone volume fraction,trabecular number,trabecular thickness,bone surface to bone volume ratio(BS/BV),and β-catenin expression compared with those of the model group(P<0.05).In contrast,the structure model index,trabecular separation,and BS/BV were significantly decreased compared with those of the ovariectomised osteoporosis model group(P<0.05).No differences were observed in the above parameters between animals of the QEP-and oestradiol-treated groups.Conclusions:The treatment mechanism of QEP in treating osteoporosis may improve the bone mass by improving the level of β-catenin,and the number of trabecular bone is improved,the number of trabecular bone is increased,the direction is parallel,the direction is consistent and the porosity decreases...