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. TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). Results:: After the Wnt signaling was inhibited by LGK974, the expression of osteoblast-related 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.

中文翻译：

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TP508 通过激活 Wnt/β-catenin 信号通路促进牵引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。其在牵张成骨的分子机制中的作用仍不清楚。本研究建立了大鼠胫骨牵张成骨（DO）模型，并探讨了TP508在DO过程中骨再生中的作用和机制。方法：：使用显微计算机断层扫描（Micro-CT）和苏木精-伊红（HE）染色来追踪成骨作用。采用蛋白质印迹和实时定量聚合酶链反应（qRT-PCR）检测成骨细胞相关因子、Wnt/β-连环蛋白信号相关蛋白和基因的表达。采用免疫组织化学法检测细胞质和细胞核中β-catenin的表达。TP508 加速骨再生，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上调β-catenin及其靶标CYCLIN-D1，并可以逆转LGK974引起的成骨能力下降。结论:: 总之，TP508 通过激活 Wnt/β-catenin 信号通路促进 DO 骨再生。