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Publication : Knockout of TLR4 promotes fracture healing by activating Wnt/β-catenin signaling pathway.

First Author  Zhao C Year  2020
Journal  Pathol Res Pract Volume  216
Issue  2 Pages  152766
PubMed ID  31796334 Mgi Jnum  J:299436
Mgi Id  MGI:6490850 Doi  10.1016/j.prp.2019.152766
Citation  Zhao C, et al. (2020) Knockout of TLR4 promotes fracture healing by activating Wnt/beta-catenin signaling pathway. Pathol Res Pract 216(2):152766
abstractText  OBJECTIVES: The aim of this study was to investigate the effect of Toll like receptor 4 (TLR4) on fracture healing. METHODS: The open tibial fracture models in TLR4 knockout (TLR4(-/-)) and wild type (WT) C57BL-6 J mice were established. The radiological examination, tartrate-resistant acid phosphatase (TRAP) staining, Micro-CT scan and biological torsion test were performed on 7, 14 and 21 days after operation. Enzyme Linked Immunosorbent Assay (ELISA) kit was used to detect the expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin 6 (IL-6). Western blotting was used to detect the expression of beta-catenin, Wingless-type MMTV integration site family, member 4 and 5B (Wnt4 and Wnt5B), proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-2 (BMP-2) of the callus tissue obtained from mice. RESULTS: TLR4 knockout promoted fracture healing, reduced the number of osteoclasts, increased bone callus volume (BV) and callus mineralized volume fraction (BV/TV%) (P < 0.05), increased the maximum torque and torsional stiffness of callus (P < 0.05), reduced TNF-alpha, IL-1beta and IL-6 expression (P < 0.01), and increased the expression levels of beta-catenin, Wnt4, Wnt5B, PCNA and BMP-2 (P < 0.01). CONCLUSION: TLR4 knockout reduced inflammatory and promoted fracture healing by activating Wnt/beta-catenin signaling pathway.
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