基于BMP-2/SMAD/Runx2通路探究骨化三醇胶囊对大鼠胫骨骨折愈合的影响  

Effect of calcitriol capsule on tibial fracture healing in rats based on BMP-2/SMAD/Runx2 pathway

作　　者：王皓[1] 凃峰[1] 赵文斌[1] 张麟 WANG Hao;TU Feng;ZHAO Wenbin;ZHANG Lin(Department of Orthopedics,the First Hospital of Wuhan,Wuhan 430022,China)

机构地区：[1]武汉市第一医院骨科,湖北武汉430022

出　　处：《中国骨质疏松杂志》2022年第1期47-51,共5页Chinese Journal of Osteoporosis

摘　　要：目的探讨骨化三醇胶囊(Cal)通过骨形态发生蛋白2(BMP-2)/SMAD/Runt相关转录因子2(Runx2)通路对大鼠胫骨骨折愈合的影响及相关机制。方法将52只SD大鼠随机分为对照组(Cont)、胫骨骨折组、Cal组(灌胃10 ng/mL Cal,连续4周)、Cal+Noggin(BMP特异抑制剂)组(灌胃10 ng/mL Cal+经皮注射50 ng/mL Noggin,连续4周)。采用X射线、全自动生化分析仪、micro CT、HE染色、Western blot分析治疗效果及可能机制。结果4周后,胫骨骨折组骨折线明显,Cal组骨折线几乎不可见,断端有大量骨痂,Cal+Noggin组骨折愈合较差。胫骨骨折组骨密度、骨体积分数、ALP、OCN、PINP水平及BMP-2、Runx2、p-SMAD1/5/8/SMAD1/5/8表达高于Cont组,骨小梁分离度低于Cont组(P<0.05)。较于胫骨骨折组,Cal组骨密度、骨体积分数、ALP、OCN、PINP水平及BMP-2、Runx2、p-SMAD1/5/8/SMAD1/5/8表达增高,骨小梁分离度降低(P<0.05)。较于Cal组,Cal+Noggin组骨密度、骨体积分数、ALP、OCN、PINP水平及BMP-2、Runx2、p-SMAD1/5/8/SMAD1/5/8表达降低,骨小梁分离度增加(P<0.05)。结论Cal可能通过激活BMP-2/SMAD/Runx2通路,改善新生骨痂骨密度及微结构,促进胫骨骨折愈合。Objective To explore the effect of calcitriol capsule(Cal)on tibial fracture healing in rats through bone morphogenetic protein-2(BMP-2)/SMAD/Runt-related transcription factor 2(Runx2)signaling pathway.Methods Fifty-two SD rats were randomly divided into control group(Cont),tibial fracture group,Cal group(gavage 10 ng/mL Cal for 4 consecutive weeks),and Cal+Noggin(BMP specific inhibitor)group(gavage 10 ng/mL Cal+percutaneous injection of 50 ng/mL Noggin for 4 consecutive weeks).X-ray,automatic biochemical analyzer,micro CT,HE staining and Western blotting were used to analyze the treatment effect and possible mechanism.Results After 4 weeks of the fractures,the fracture line in the tibial fracture group was obvious.The fracture line in the Cal group was almost invisible and there was a lot of callus at the broken end.The fracture healing in the Cal+Noggin group was poor.Bone mineral density,bone volume fraction,levels of ALP,OCN,PINP and the protein levels of BMP-2,Runx2,and p-SMAD1/5/8/SMAD1/5/8 in the tibial fracture group were higher than those in the Cont group(P<0.05),while trabecular separation was lower than that in the Cont Group(P<0.05).Compared to those in the tibial fracture group,bone mineral density,bone volume fraction,levels of ALP,OCN,PINP,and the protein levels of BMP-2,Runx2,and p-SMAD1/5/8/SMAD1/5/8 in the Cal group increased,and trabecular separation decreased(P<0.05).Compared to those in the Cal group,bone mineral density,bone volume fraction,levels of ALP,OCN,PINP,and the protein levels of BMP-2,Runx2,and p-SMAD1/5/8/SMAD1/5/8 in the Cal+Noggin group decreased,and trabecular separation increased(P<0.05).Conclusion Cal may improve bone mineral density and microstructure of new callus,and promote the healing of tibial fractures by activating BMP-2/SMAD/Runx2 pathway.

关 键 词：骨化三醇胶囊 胫骨 骨折愈合 骨形态发生蛋白2 SMAD Runt相关转录因子2 

分 类 号：R681[医药卫生—骨科学] R965[医药卫生—外科学]