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Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs

  • Authors:
    • Shenghong Li
    • Zhenqiang Xiong
    • Yuxin Lan
    • Qian Zheng
    • Li Zhang
    • Xiaomei Xu
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    Affiliations: Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 67
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    Published online on: June 25, 2024
       https://doi.org/10.3892/ijmm.2024.5391
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Abstract

Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. For this purpose, a protein‑protein interaction network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression levels were evaluated by reverse transcription‑quantitative and western blotting. Alizarin red and alkaline phosphatase staining were also employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co‑localization of NAR molecular probes and AKT in cells. The repair of mandibular defects was assessed by micro‑computed tomography (micro‑CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein, AKT. The results demonstrated that activation of the nitric oxide (NO)‑cyclic guanosine monophosphate (cGMP)‑protein kinase G (PKG) signaling pathway could promote the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated the ability of NAR to promote the osteogenic differentiation of hPDLSCs. Micro‑CT and Masson staining revealed that the NAR gavage group exhibited more new bone formation at the defect site. Immunofluorescence assays confirmed the upregulated expression of Runt‑related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the results of the present study suggested that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO‑cGMP‑PKG signaling pathway through its binding to AKT.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Xiong Z, Lan Y, Zheng Q, Zhang L and Xu X: Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs. Int J Mol Med 54: 67, 2024.
APA
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., & Xu, X. (2024). Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs. International Journal of Molecular Medicine, 54, 67. https://doi.org/10.3892/ijmm.2024.5391
MLA
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., Xu, X."Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs". International Journal of Molecular Medicine 54.2 (2024): 67.
Chicago
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., Xu, X."Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs". International Journal of Molecular Medicine 54, no. 2 (2024): 67. https://doi.org/10.3892/ijmm.2024.5391
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Xiong Z, Lan Y, Zheng Q, Zhang L and Xu X: Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs. Int J Mol Med 54: 67, 2024.
APA
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., & Xu, X. (2024). Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs. International Journal of Molecular Medicine, 54, 67. https://doi.org/10.3892/ijmm.2024.5391
MLA
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., Xu, X."Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs". International Journal of Molecular Medicine 54.2 (2024): 67.
Chicago
Li, S., Xiong, Z., Lan, Y., Zheng, Q., Zhang, L., Xu, X."Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs". International Journal of Molecular Medicine 54, no. 2 (2024): 67. https://doi.org/10.3892/ijmm.2024.5391
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