A hypothesis of mesenchymal stem cell osteogenic differentiation mediated by chelidonic acid through the calcium import: original research and computer simulation.

Chelidonic acid (ChA) is small molecule capable of inducing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and the formation of mineralized bone matrix (MBM) both in vitro and in vivo. However, the molecular mechanisms underlying these effects are unknown. Therefore, in silico...

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Publicado en:Histochemistry & Cell Biology Vol. 163; no. 1; pp. 1 - 14
Autores principales: Nasibov, Temur, Gorokhova, Anna, Porokhova, Ekaterina, Shupletsova, Valeria, Yurova, Kristina, Avdeeva, Elena, Bariev, Usman, Litvinova, Larisa, Belousov, Mikhail, Khlusov, Igor
Formato: Journal Article
Publicado: Springer Nature 2025
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Springer Nature
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        10.1007/s00418-024-02342-5
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        atl: A hypothesis of mesenchymal stem cell osteogenic differentiation mediated by chelidonic acid through the calcium import: original research and computer simulation.
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          Nasibov, Temur
          Gorokhova, Anna
          Porokhova, Ekaterina
          Shupletsova, Valeria
          Yurova, Kristina
          Avdeeva, Elena
          Bariev, Usman
          Litvinova, Larisa
          Belousov, Mikhail
          Khlusov, Igor
        affil: https://ror.org/01yecy831 Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University, 634050, Tomsk, Russian Federation
      sug:
      ab: Chelidonic acid (ChA) is small molecule capable of inducing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and the formation of mineralized bone matrix (MBM) both in vitro and in vivo. However, the molecular mechanisms underlying these effects are unknown. Therefore, in silico modelling of potential molecular targets of ChA was performed. ChA was isolated from Saussurea controversa. The ability of ChA to induce in vitro differentiation MSCs into osteoblasts synthesizing MBM was detected using alizarin red staining. ChA osteogenic activity was studied in mice by in situ test of ectopic osteogenesis, using the subcutaneous implantation of syngeneic bone marrow on the calcium phosphate coated titanium plates. DIGEP-Pred web service was used to simulate in silico the effect of ChA on gene expression, and overrepresentation analysis to search for common ontologies and pathways. ChA linearly increased the number of single (R2 = 0.92, p = 0.039) and the total areas of MBM sites (R2 = 0.96, p = 0.019) in a 21-day MSC culture. Oral administration of ChA led to two to three times improved bone and bone marrow formation in situ. In silico modelling identified 306 genes (including 7 calcium import genes) and 9 signalling pathways potentially involved in ChA osteogenic effect and calcium metabolism in MSCs. In silico analysis revealed a list of key signalling pathways and genes for calcium influx into MSCs and their differentiation into osteoblasts as the first target candidates for studying real gene expression and molecular mechanisms of the ChA osteogenic effects.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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