TP508 Promotes Bone Regeneration on Distraction Osteogenesis via the Activation of Wnt/β-catenin Signaling Pathway.

IF 2.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kehan Li, Linan Liu, Jingyi Zhang, Chenyu Liao, Jian Hu, Jian Song
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引用次数: 0

Abstract

Introduction: TP508 is a thrombin peptide that participates in the inflammatory response and wound healing. Its role in the molecular mechanism of distraction osteogenesis remains unclear. This study established a tibia distraction osteogenesis (DO) model in rats and investigated the role and mechanism of TP508 in bone regeneration during DO.

Method: Micro-computed tomography (Micro-CT) and hematoxylin-eosin (HE) staining were used to track osteogenesis. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to measure the expression of osteoblast-related factors, Wnt/β- catenin signaling-related proteins and genes. Immunohistochemistry was used to measure the expression of β-catenin in the cytoplasm and nucleus.

Results: TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). After the Wnt signaling was inhibited by LGK974, the expression of osteoblastrelated factors was downregulated, leading to a decrease in bone regeneration ability. More importantly, TP508 upregulated β-catenin and its target CYCLIN-D1 and could reverse the decreased osteogenic ability caused by LGK974.

Conclusion: In conclusion, TP508 promotes bone regeneration in DO by activating the Wnt/β- catenin signaling pathway.

TP508通过激活Wnt/β-catenin信号通路促进牵引性成骨过程中的骨再生
简介TP508 是一种凝血酶肽,参与炎症反应和伤口愈合。它在牵张成骨的分子机制中的作用尚不清楚。本研究建立了大鼠胫骨牵张成骨(DO)模型,并探讨了TP508在DO过程中骨再生的作用和机制:方法:采用显微计算机断层扫描(Micro-CT)和苏木精-伊红(HE)染色追踪骨生成。Western印迹和定量实时聚合酶链反应(qRT-PCR)用于检测成骨细胞相关因子、Wnt/β- catenin信号相关蛋白和基因的表达。免疫组化技术用于检测β-catenin在细胞质和细胞核中的表达。TP508加速了骨再生,增加了成骨细胞相关因子碱性磷酸酶(ALP)、runt相关转录因子2(RUNX2)和骨钙素(OCN)的表达:结果:LGK974抑制Wnt信号传导后,成骨细胞相关因子表达下调,导致骨再生能力下降。更重要的是,TP508能上调β-catenin及其靶标CYCLIN-D1,并能逆转LGK974导致的成骨能力下降:总之,TP508可通过激活Wnt/β- catenin信号通路促进DO的骨再生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current pharmaceutical biotechnology
Current pharmaceutical biotechnology 医学-生化与分子生物学
CiteScore
5.60
自引率
3.60%
发文量
203
审稿时长
6 months
期刊介绍: Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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