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

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

Volume: 25

Author(s): Kehan Li, Linan Liu, Jingyi Zhang, Chenyu Liao, Jian Hu*Jian Song*

Affiliation:

• The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China

• State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

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. 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.

Cite this article as:

Li Kehan, Liu Linan, Zhang Jingyi, Liao Chenyu, Hu Jian*, Song Jian*, TP508 Promotes Bone Regeneration on Distraction Osteogenesis via the Activation of Wnt/β-catenin Signaling Pathway, Current Pharmaceutical Biotechnology 2024; 25 () . https://dx.doi.org/10.2174/0113892010289575240306033011