Effect And Mechanism Of Arbutin On Ovariectomized Osteoporotic Mice

Objectives: Arbutin is an extractable polyphenolic compound found in natural plants,which has been widely reported in the literature to have a variety of biological activities and medicinal values.Some studies have tentatively shown that arbutin can promote the differentiation of MC3T3-E1 cells,thereby promoting the proliferation of osteoblasts,and has a good safety profile.In this experiment,to investigate the effects and mechanisms of arbutin on mice with depressed osteoporosis,we first established an osteoporosis model,and then determined the expression of key indicators in the proliferation and differentiation pathways of osteoblasts and the alteration of bone microstructure by tissue serology and immunohistochemical staining,in order to provide a theoretical basis for the treatment of primary osteoporosis with arbutin.Methods: Eighteen female C57BL/6 mice(8 weeks old)were randomly divided into three groups: sham-operated group(Sham),osteoporosis model group(OVX)and arbutin-intervened osteoporosis model group(A+OVX).The arbutin intervention osteoporosis model group was treated with arbutin 200 mg/kg/d after 1 week of modeling.The same volume of 0.9% saline was injected intraperitoneally into the sham-operated and osteoporosis groups,and each group was given continuous intervention for 8 weeks.1.Bone mineral density(BMD)was measured by dual-energy X-ray absorptiometry.2.Changes in bone microstructure,including distal femoral trabeculae,were observed in mice by Micro-CT;osteocalcin(OCN)was measured in peripheral venous blood of mice by a special osteocalcin kit and ELISA and alkaline phosphatase(ALP)secretion in peripheral venous blood of mice.(4)The number and distribution of bone trabeculae in the distal femoral tissue were observed by HE staining,and the expression of Runx2 andβ-catenin in the distal femoral epiphysis were observed by immunohistochemical staining.(5)SPSS 22.0 software was used for statistical analysis,and the measured data were expressed as mean ± standard deviation(X ± SD),and ANOVA was used for comparison between groups,and P < 0.05 was considered statistically significant.Results: 1.Compared to the osteoporosis model group,bone mineral density(BMD)was significantly increased in the arbutin intervention group.2.Bone microstructure showed that arbutin increased BV/TV(trabecular volume ratio),Tb.N(trabecular number)and Tb.Th(trabecular thickness),and effectively decreased Tb.sp.3.Compared with the Sham group,serum osteocalcin and alkaline phosphatase levels in the osteoporosis model group were significantly reduced,but there was no significant change in the arbutin intervention group.4.HE staining analysis showed that arbutin inhibited osteoporosis-induced bone loss.In addition,immunohistochemistry analysis showed that arbutin increased the expression of β-catenin and Runx2 protein in the distal femoral metaphyseal of osteoporotic mice.Conclusion: We demonstrated that arbutin could effectively increase bone mineral density throughout the body and reduce bone trabecula loss in model mice.The mechanism was that arbutin promoted Runx2 and β-catenin expression in the osteoblast differentiation signaling pathway,which promoted osteoblasts maturation and played an anti-osteoporosis role.It also provides a potential drug for the treatment and prevention of osteoporosis.