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甲状旁腺激素通过 Notch 信号通路促进兔胫骨骨折愈合。

PTH promotes rabbit tibial fracture healing via the Notch signaling pathway.

机构信息

Department of Orthopedics, First People's Hospital of Fuyang District, Hangzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1616-1623. doi: 10.26355/eurrev_202002_20336.

DOI:10.26355/eurrev_202002_20336
PMID:32141528
Abstract

OBJECTIVE

To explore the effect of parathyroid hormone (PTH) on the expression of Jagged1 in the rabbit tibial fracture healing, and its function and mechanism in this process via the Notch signaling pathway.

MATERIALS AND METHODS

A total of 60 New Zealand white rabbits were randomly divided into control group (n=30) and experimental group (n=30). Then, a rabbit tibial fracture model was established. After surgery, the rabbits in experimental group were given 10 μg/kg PTH (1-34) once a day for 5 days a week, while those in control group were given an equal volume of normal saline. Six rabbits were randomly selected from each group at 1, 2, 3, 4, and 6 weeks after surgery to collect right tibia specimens. Next, X-ray examination, bone mineral density (BMD) test, histological detection, and serum biochemical test were performed. Additionally, the messenger ribonucleic acid (mRNA) expression levels of Notch1 and Jagged1 in the Notch signaling pathway were measured via polymerase chain reaction (PCR) assay. Their protein levels were detected through Western blotting analysis.

RESULTS

The healing and BMD in experimental group were better than those in control group since cortical and medullary bridging was observed in the rabbits of experimental group at the 6th week after surgery. Plasma level of alkaline phosphatase (ALP), P content, and the product of Ca and P significantly increased (p<0.05) in experimental group. The pathological morphology of the calluses stained with hematoxylin-eosin (HE) in experimental group was overtly superior to that in control group. The PCR results revealed that both mRNA and protein levels of Notch1 and Jagged1 were lower in control group than those in experimental group (p<0.05).

CONCLUSIONS

PTH (1-34) promotes the rabbit tibial fracture healing by regulating Jagged1 ligand molecules in the Notch signaling pathway.

摘要

目的

通过 Notch 信号通路探讨甲状旁腺激素(PTH)对兔胫骨骨折愈合过程中 Jagged1 表达的影响及其在该过程中的作用和机制。

材料与方法

将 60 只新西兰大白兔随机分为对照组(n=30)和实验组(n=30),建立兔胫骨骨折模型。术后实验组给予 10μg/kg PTH(1-34),1 次/d,每周 5 天,对照组给予等量生理盐水。术后 1、2、3、4、6 周,每组各随机取 6 只兔子,取右侧胫骨标本。行 X 线检查、骨密度(BMD)检测、组织学检测和血清生化检测,采用聚合酶链反应(PCR)法检测 Notch 信号通路中 Notch1、Jagged1 的信使核糖核酸(mRNA)表达水平,采用 Western blot 分析检测其蛋白水平。

结果

实验组骨折愈合和 BMD 优于对照组,术后第 6 周实验组兔子可见皮质和髓腔桥接。实验组碱性磷酸酶(ALP)、P 含量和 Ca、P 乘积显著升高(p<0.05)。实验组 HE 染色骨痂的病理形态明显优于对照组。PCR 结果显示,对照组 Notch1、Jagged1 的 mRNA 和蛋白水平均低于实验组(p<0.05)。

结论

PTH(1-34)通过调节 Notch 信号通路中的 Jagged1 配体分子促进兔胫骨骨折愈合。

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