Pro-differentiative, Pro-adhesive and Pro-migratory Activities of Isorhamnetin in MC3T3-E1 Osteoblasts via Activation of ERK-dependent BMP2-Smad Signaling.

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  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9701934 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0283 (Electronic) Linking ISSN: 10859195 NLM ISO Abbreviation: Cell Biochem Biophys Subsets: MEDLINE
    • Publication Information:
      Original Publication: Totowa, NJ : Humana Press, c1996-
    • Subject Terms:
      Osteoblasts*/metabolism ; Osteoblasts*/drug effects ; Osteoblasts*/cytology ; Bone Morphogenetic Protein 2*/metabolism ; Cell Differentiation*/drug effects ; Cell Movement*/drug effects ; Quercetin*/pharmacology ; Quercetin*/analogs & derivatives ; Cell Adhesion*/drug effects ; Signal Transduction*/drug effects; Animals ; Mice ; Cell Line ; Smad Proteins/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Osteogenesis/drug effects ; MAP Kinase Signaling System/drug effects
    • Abstract:
      Osteoporosis (OP) is an epidemic bone remodeling disorder of growing relevance with the aging population. Considering that isorhamnetin (ISO), a flavonoid derived from plant, has been newly reckoned as an active ingredient in treating OP, our paper was conducted to investigate the regulatory role and mechanism of ISO in OP. CCK-8 method detected cell activity. Alkaline phosphatase (ALP) assay kit, ALP staining and alizarin red S staining measured osteogenic differentiation. RT-qPCR and Western blot examined the expressions of osteoblast-related proteins. Wound healing and cell adhesion assays severally detected cell migration and adhesion. Also, Western blot tested the expressions of extracellular signal-regulated kinase (ERK) signaling-associated proteins. As illustrated, after MC3T3-E1 pre-osteoblasts were stimulated to differentiate to osteoblasts, ISO markedly promoted the differentiation, mineralization, migration and adhesion of MC3T3-E1 osteoblasts in a concentration-dependent manner. In addition, administration of ISO functioned as an activator of ERK-dependent BMP2-Smad signaling in MC3T3-E1 osteoblasts and pretreatment with ERK inhibitor PD98059 partially compensated the impacts of ISO on MC3T3-E1 osteoblasts differentiation, mineralization, migration as well as adhesion. To be summarized, ISO might activate ERK-dependent BMP2-Smad signaling to facilitate the differentiation, mineralization, migration and adhesion of MC3T3-E1 osteoblasts, suggesting the protective potential of ISO in OP.
      Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests.
      (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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    • Grant Information:
      UM0122009 UMCARE Research Fund
    • Contributed Indexing:
      Keywords: Adhesion; ERK signaling; MC3T3-E1 preosteoblasts; isorhamnetin; osteogenic differentiation
    • Accession Number:
      0 (Bone Morphogenetic Protein 2)
      9IKM0I5T1E (Quercetin)
      07X3IB4R4Z (3-methylquercetin)
      0 (Smad Proteins)
      EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
      0 (Bmp2 protein, mouse)
    • Publication Date:
      Date Created: 20240813 Date Completed: 20241119 Latest Revision: 20241212
    • Publication Date:
      20241212
    • Accession Number:
      10.1007/s12013-024-01450-2
    • Accession Number:
      39136840