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BMC veterinary research2014; 10; 173; doi: 10.1186/s12917-014-0173-z

Nestin expression in mesenchymal stromal cells: regulation by hypoxia and osteogenesis.

Abstract: The intermediate filament protein nestin is used as a marker for neural stem cells, and its expression is inversely correlated with cellular differentiation. More recently, nestin expression has also been described in other cell types including multipotential mesenchymal stromal cells (MSCs). In this study, we examined the expression of nestin in equine, canine and human bone marrow-derived MSCs undergoing osteogenic differentiation, to determine whether nestin levels were attenuated as the cells acquired a more mature phenotype. In addition, the expression of nestin may be under the influence of cellular hypoxia, as nestin expression is known to increase in areas of ischemic tissue damage. Therefore, we also examined the effects of hypoxia on expression of nestin in human MSCs and examined a role for hypoxia inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the response. Additionally, we quantified the temporal expression of nestin in the fracture callus during bone regeneration, a site that has been characterized as hypoxic. Results: There were no significant changes in nestin expression in MSCs during osteogenic differentiation. There was a significant increase in expression of nestin mRNA and protein in human MSCs in response to hypoxia (1% O2) or the chemical hypoxia mimetic desferroxamine. This may be due to upregulation of VEGF under hypoxia, as treatment of cells with the VEGF receptor antagonist CPO-P11 attenuated hypoxia-induced nestin expression. A significant increase in nestin mRNA expression was observed in the fracture callus of mice three and seven days post fracture. Conclusions: Nestin was not a selective marker for MSCs, as its expression was maintained during osteogenic differentiation, in all species examined. Furthermore our data suggest that nestin expression can be induced by hypoxia, and that this increase in nestin is partially regulated by HIF-1α and VEGF. Interestingly, nestin levels were significantly upregulated at the fracture site. Further studies are required to understand the role of nestin in bone cell biology and ultimately bone regeneration.
Publication Date: 2014-08-05 PubMed ID: 25088159PubMed Central: PMC4236815DOI: 10.1186/s12917-014-0173-zGoogle Scholar: Lookup
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  • Journal Article
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Summary

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The article explores the interaction between hypoxia, osteogenesis, and the expression of the protein nestin in mesenchymal stromal cells (MSCs). The researchers found that nestin levels do not change significantly during maturation of the cells, but can be triggered by hypoxia, the state of oxygen shortage in the body.

Study Goals and Approach

  • The primary objective of the study was to investigate whether mature (differentiated) MSCs, derived from equine, canine and humans, show altered levels of the protein nestin.
  • Nestin, a recognized marker for neural stem cells, had thus far been considered inversely collected with cellular differentiation, hence noticing it in differentiated cells entailed rethinking its role.
  • The researchers speculated that nestin expression might be affected by cellular hypoxia, given previous studies linking increased nestin expression to areas of ischemic tissue injury.
  • To investigate the relationship between hypoxia and nestin, they studied the protein’s expression under hypoxic conditions, considering factors such as Hypoxia-Inducible Factor 1-alpha (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) in their assessments.
  • They also investigated the pattern of expression of nestin in mouse fracture callus (part of the healing process in fractures) which is known to be a hypoxic environment.

Research Findings

  • Nestin expression did not show significant changes in MSCs during their differentiation into bone cells (osteogenic differentiation).
  • Under hypoxic conditions or when using the chemical hypoxia mimetic desferroxamine, there was a marked increase in the production of nestin mRNA and protein in human MSCs.
  • This increase in nestin might be when the amount of VEGF in the cells increases under hypoxic conditions, and treating the cells with a VEGF antagonist reduced the hypoxia-induced nestin expression.
  • A significant rise in nestin mRNA expression was noticed in the fracture callus of mice three and seven days post-fracture.

Conclusions and Future Directions

  • The study found that, contrary to previous belief, nestin is not selectively expressed in MSCs, as its levels remained steady during osteogenic differentiation in all species observed.
  • The research also established that hypoxic conditions can induce the expression of nestin, and this induction is partially regulated by two factors: HIF-1α and VEGF.
  • Additionally, nestin levels were observed to increase significantly at the fracture site, marking an area for further exploration of nestin’s role in bone cell biology and bone regeneration.
  • The researchers suggest further studies to fully understand nestin’s role in these contexts.

Cite This Article

APA
Wong A, Ghassemi E, Yellowley CE. (2014). Nestin expression in mesenchymal stromal cells: regulation by hypoxia and osteogenesis. BMC Vet Res, 10, 173. https://doi.org/10.1186/s12917-014-0173-z

Publication

ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 10
Pages: 173

Researcher Affiliations

Wong, Alice
    Ghassemi, Ehssan
      Yellowley, Clare E

        MeSH Terms

        • Animals
        • Bone Marrow Cells / metabolism
        • Cells, Cultured
        • Fracture Healing / physiology
        • Fractures, Bone / metabolism
        • Gene Expression Regulation / physiology
        • Humans
        • Mesenchymal Stem Cells / metabolism
        • Nestin / genetics
        • Nestin / metabolism
        • Osteogenesis / physiology
        • Oxygen / pharmacology
        • Species Specificity

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