Journals / Acta Orthopaedica et Traumatologica Turcica / 2020 / Cilt: 54 - Sayı: 3

Effect of kirenol on the interaction between the WNT/ β-Catenin and RUNX2/TCF/LEF1 pathways in fracture healing in vivo

Pages
320–329
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: Kirenol may improve fracture healing in a dose-dependent manner with the early activation of the Wnt/β-catenin pathway and the activation of the Runx-2 pathway.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: This study aimed to determine the effects of a natural diterpenoid, kirenol, on fracture healing in vivo in an experimental rat model of femur fracture and investigate its potential mechanism of action via the Wnt/β-catenin pathway.
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Key Findings & Data:Methods: In this study, 64 male Wistar albino rats aged 5-7 weeks and weighing 261–348 g were randomly divided into 8 groups from A to L, with eight rats in each group.
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Conclusion & Impact:Conclusion: Kirenol may improve fracture healing in a dose-dependent manner with the early activation of the Wnt/β-catenin pathway and the activation of the Runx-2 pathway.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Özet

Objective: This study aimed to determine the effects of a natural diterpenoid, kirenol, on fracture healing in vivo in an experimental rat model of femur fracture and investigate its potential mechanism of action via the Wnt/β-catenin pathway. Methods: In this study, 64 male Wistar albino rats aged 5-7 weeks and weighing 261–348 g were randomly divided into 8 groups from A to L, with eight rats in each group. Standardized fractures were created in the right femurs of the rats and then fixed with an intramedullary Kirschner wire. Four experimental groups were administered 2 mg/kg/ day kirenol (Groups C and G) and 4 mg/kg/day (Groups D and H) kirenol by oral gavage.Thereafter, the animals were sacrificed at two time points as follows: on the 10th day (Groups B, C and D) and on the 21st day (Groups F, G and H) after the surgery; fracture healing in each group was assessed radiologically and histopathologically. The Radiographic Union scale of tibia fracture scoring system was used in the radiological examination; callus volume and density were measured using computed tomography. In the histopathologic examination, the scoring system described by Huo et al. was used. Additionally, the mechanism of action was evaluated based on the analyses of protein expression of Wnt3a, LRP5, TCF-LEF1, β-catenin, and Runx-2 proteins using western blot analysis. Results: Among the animals sacrificed on the 10th day after the surgery, the highest histopathological and radiological scores were observed in Group D (p 0.05). The callus volume and density were the highest in Groups G and H, respectively, although the differences among groups were not significant. Conclusion: Kirenol may improve fracture healing in a dose-dependent manner with the early activation of the Wnt/β-catenin pathway and the activation of the Runx-2 pathway.

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Cite This Article

KARAMAN, İ., GÜNAY, A. E., YERER, M. B., DEMİRPOLAT, E., DOĞAN, S., YAY, A. H., KAFADAR, İ. H. (2020). Effect of kirenol on the interaction between the WNT/ β-Catenin and RUNX2/TCF/LEF1 pathways in fracture healing in vivo. Acta Orthopaedica et Traumatologica Turcica, Cilt: 54 - Sayı: 3, 320–329. https://ajindex.com/articles/144422

References (15)

  1. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop 1998
  2. [Crossref] 2. LaVelle DG. Delayed union and nonunion of fractures. In: Canale S.T. ed. Campbell’s Operative Orthopaedics (10th ed), Philadelphia, Mosby Publishers. 2003
  3. pp.3126. 3. Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982
  4. [Crossref] 4. He S, Lu Y, Liu X, et al. Wnt3a: functions and implications in cancer. Chin J Cancer 2015
  5. [Crossref] 5. McDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009
  6. [Crossref] 6. Nusse R, Varmus H. Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO J 2012
  7. [Crossref] 7. Byun MR, Hwang JH, Kim AR, et al. Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. Cell Death Differ 2014
  8. [Crossref] 8. Shu B, Zhang M, Xie R, et al. BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development. J Cell Sci 2011
  9. [Crossref] 9. Lian JB, Javed A, Zaidi SK, et al. Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr 2014
  10. [Crossref] 10. Xiao J, Yang R, Yang L, et al. Kirenol attenuates experimental autoimmune encephalomyelitis by ınhibiting differentiation of Th1 and Th17 cells and inducing apoptosis of effector T cells. Sci Rep 2015
  11. doi: 10.1038/srep09022. [Crossref] 11. Jiang Z, Yu QH, Cheng Y, Guo XJ. Simultaneous quantification of eight major constituents in Herba Siegesbeckiae by liquid chromatography coupled with electrospray ionization time-offlight tandem mass spectrometry. J Pharm Biomed Anal 2011
  12. [Crossref] 12. Wang JP, Zhou YM, Ye YJ, et al. Topical anti-inflammatory and analgesic activity of kirenol isolated from Siegesbeckia orientalis. J Ethnopharmacol 2011
  13. [Crossref] 13. Bi J, Xin HL, Lin ZF, et al. Effect of kirenol on cytokines in serum and apoptosis proteins expression in synoviocytes of adjuvant arthritis rats. Chinese Traditional and Herbal Drugs 2007
  14. Kim MB, Song Y, Kim C, Hwang JK. Kirenol inhibits adipogenesis through activation of theWnt/β-catenin signaling pathway in T3-L1 adipocytes. Biochem Biophys Res Commun 2014
  15. [Crossref] 15. Lua Y,