L-白雀木醇通过激活Wnt/β-catenin信号通路促进骨折愈合  

L-quebrachitol promotes fracture healing by activating Wnt/β-catenin signaling pathway

作　　者：白立曦[1] 许静[1] 段鹏 谢万科 徐之超[1] 杜俊凯[1] BAI Lixi;XU Jing;DUAN Peng;XIE Wanke;XU Zhichao;DU Junkai(Emergency Center,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院急诊中心,西安710061

出　　处：《山西医科大学学报》2023年第10期1381-1388,共8页Journal of Shanxi Medical University

基　　金：陕西省自然科学基础研究计划项目(2018JM7152)。

摘　　要：目的考察L-白雀木醇(L-quebrachitol,L-Q)对骨折愈合的促进作用及其对Wnt/β-catenin信号通路的影响。方法将40只大鼠随机分为对照组(1%DMSO)和白雀木醇组[L-Q,30 mg/(kg·d)白雀木醇],每组20只,给药4周后对大鼠进行安全性评价。构建胫骨骨折大鼠模型,然后将36只胫骨骨折模型大鼠随机分为3组:模型组(1%DMSO)、10 mg/(kg·d)L-白雀木醇组(10L-Q组)和30 mg/(kg·d)L-白雀木醇组(30L-Q组),每组12只。给药3周后,对各组大鼠进行X线检查和Mirco-CT分析及骨痂组织番红O-固绿染色。通过qRT-PCR或Western blot检测骨痂组织中骨钙素(OCN)、骨桥蛋白(OPN)、Runt相关转录因子-2(Runx2)、碱性磷酸酶(ALP)、骨形态发生蛋白-2(BMP-2)、Wnt-3a、Wnt-5a、β-catenin和糖原合成酶激酶-3β(GSK-3β)的表达。结果对照组和L-Q组大鼠的外观和行为、体质量和摄食量、血液学指标、血清生化指标、脏器系数无显著差异(P>0.05)。与模型组相比,10L-Q组和30L-Q组大鼠的骨痂内新生骨小梁和成骨分化明显增多,伴随骨痂跨越骨折端和编织骨替代软骨细胞。与模型组相比,10L-Q组和30L-Q组大鼠骨痂组织中OCN、OPN、Runx2、ALP和BMP-2的mRNA相对表达水平均升高(P<0.05)。与模型组相比,10L-Q组和30L-Q组大鼠骨痂组织中Wnt-3a、Wnt-5a和β-catenin的mRNA和蛋白相对表达水平均升高(P<0.05),GSK-3β的mRNA和蛋白相对表达水平均降低(P<0.05)。结论L-白雀木醇可促进胫骨骨折大鼠骨折愈合,其机制可能与Wnt/β-catenin信号通路的激活有关。Objective To investigate the promoting effect of L-quebrachitol(L-Q)on the fracture healing and its effect on Wnt/β-catenin signaling pathway.Methods Forty rats were randomly divided into control group(1%DMSO)and L-Q group[30 mg/(kg·d)L-quebrachitol],with 20 rats in each group,and the safety was evaluated after four weeks of administration.A rat model of tibia fracture was constructed,and 36 tibial fracture model rats were randomly divided into three groups:model group(1%DMSO),10 mg/(kg·d)L-quebrachitol group(10L-Q group)and 30 mg/(kg·d)L-quebrachitol group(30L-Q group),with 12 rats in each group.After three weeks of administration,X-ray examination,Mirco-CT analysis and Safranin O-fast green staining of callus tissue were performed in each group.The mRNA or protein expressions of osteocalcin(OCN),osteopontin(OPN),Runt-related transcription factor-2(Runx2),alkaline phosphatase(ALP),bone morphogenetic protein-2(BMP-2),Wnt-3a,Wnt-5a,β-catenin and glycogen synthase kinase-3β(GSK-3β)in callus were detected by qRT-PCR or Western blot.Results There were no significant differences in appearance and behavior,body weight and food intake,hematological indexes,serum biochemical indexes,and organ coefficients between control group and L-Q group(P>0.05).Compared with model group,the new bone trabeculae in the callus and the osteogenic differentiation were significantly increased in 10L-Q group and 30L-Q group,accompanied by callus crossing the fracture site and braided bone instead of chondrocytes.Compared with model group,the relative expression levels of OCN,OPN,Runx2,ALP and BMP-2 mRNA in callus tissue of rats in 10L-Q group and 30L-Q group were all increased(P<0.05).Compared with model group,the relative expression levels of Wnt-3a,Wnt-5a andβ-catenin mRNA and protein in the callus tissue were increased in 10L-Q group and 30L-Q group(P<0.05),and the relative expressions of GSK-3βmRNA and protein were decreased(P<0.05).Conclusion L-quebrachitol can promote the fracture healing in rats with tibial fractures,which m

关 键 词：L-白雀木醇 骨折 愈合 成骨分化 WNT/Β-CATENIN信号通路 

分 类 号：R683.4[医药卫生—骨科学]