Human β‐defensins differently affect proliferation, differentiation, and mineralization of osteoblast‐like MG63 cells

Kraus, Dominik; Deschner, James; Jäger, Andreas; Wenghoefer, Matthias; Bayer, Stefan; Jepsen, Søren; Allam, Jean‐Pierre; Novak, Natalija; Meyer, Rainer; Winter, Jochen

doi:10.1002/jcp.22808

Cited by 56 publications

(60 citation statements)

References 44 publications

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“…HBD-2 and hBD-3 enhance the proliferation of osteoblast-like cells. Additionally, hBD-2 has a strong impact on the maturation of premature osteoblasts [15]. Furthermore, hBD-1, -2, and -3 have been demonstrated to stimulate the proliferation of tumor cells in vitro [16] (Figure 4).…”

Section: Tissue Reorganization and Wound Healingmentioning

confidence: 97%

“…Furthermore, hBD-1, -2, and -3 have been demonstrated to stimulate the proliferation of tumor cells in vitro [16] (Figure 4). Apart from that, the gene products of human β-defensins cross-regulate their own gene expression [15,16]. Tissue regeneration is closely associated with wound healing.…”

Section: Tissue Reorganization and Wound Healingmentioning

confidence: 99%

“…Recently, it has been demonstrated that human β-defensins are involved in bisphosphonate-associated osteochemonecrosis of the jawbone [13]. Furthermore, these antimicrobial peptides are able to affect their own genes-either directly or indirectly by modulating gene activity and secretion of cytokines, which in consequence leads to feedback mechanisms on defensin genes [4,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…These cellular functions are dependent on an activated epidermal growth factor receptor [19,20]. HBDs also stimulate proliferation in various human cancer cells in vitro [15,16]. Human β-defensin-2 is involved in bone cell differentiation and mineralization of osteoblast-like cells [15].…”

Section: Introductionmentioning

confidence: 99%

“…HBDs also stimulate proliferation in various human cancer cells in vitro [15,16]. Human β-defensin-2 is involved in bone cell differentiation and mineralization of osteoblast-like cells [15]. Human defensins even seem to play a role in reproduction.…”

Section: Introductionmentioning

confidence: 99%

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Human Defensins: Potential Tools for Clinical Applications

Winter

Wenghoefer

2012

Polymers

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As components of the innate immune system, antimicrobial peptides in the form of human defensins play an important role in host defense by serving as the epithelial layer’s biochemical barrier against local infections. Recent studies have shown these molecules to have far more additional cellular functions besides their antimicrobial activity. Defensins play a role in cell division, attraction and maturation of immune cells, differentiation and reorganization of epithelial tissues, wound healing and tumor suppression. This multitude of function makes human defensins appear to be excellent tools for therapeutic approaches. These antimicrobial peptides may be used directly as a remedy against bacterial and viral infections. Furthermore, the application of human defensins can be used to promote wound healing and epithelial reorganization. In particular, human β-defensins have a strong impact on osteoblast proliferation and differentiation. Human β-defensins have already been applied as a vaccination against HIV-1. Another potentially useful characteristic of defensins is their suitability as diagnostic markers in cancer therapy. In particular, α-defensins have already been used for this purpose. Human α-defensin-3, for example, has been described as a tumor marker for lymphocytes. High gene expression levels of α-defensin-3 and -4 have been detected in benign oral neoplasia, α-defensin-6 is considered to be a tumor marker for colon cancer.

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Section: Tissue Reorganization and Wound Healingmentioning

confidence: 97%

Section: Tissue Reorganization and Wound Healingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human Defensins: Potential Tools for Clinical Applications

Winter

Wenghoefer

2012

Polymers

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Characterization of Notch Signaling During Osteogenic Differentiation in Human Osteosarcoma Cell Line MG63

Ongaro

Pellati

Bagheri

et al. 2016

Journal Cellular Physiology

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Osteogenic differentiation is a multi-step process controlled by a complex molecular framework. Notch is an evolutionarily conserved intercellular signaling pathway playing a prominent role in cell fate and differentiation, although the mechanisms by which this pathway regulates osteogenesis remain controversial. This study aimed to investigate, in vitro, the involvement of Notch pathway during all the developmental stages of osteogenic differentiation in human osteosarcoma cell line MG63. Cells were cultured in basal condition (control) and in osteoinductive medium (OM). Notch inhibitors were also added in OM to block Notch pathway. During osteogenic differentiation, early (alkaline phosphatase activity and collagen type I) and late osteogenic markers (osteocalcin levels and matrix mineralization), as well as the gene expression of the main osteogenic transcription factors (Runx2, Osterix, and Dlx5) increased. Time dependent changes in the expression of specific Notch receptors were identified in OM versus control with a significant reduction in the expression of Notch1 and Notch3 receptors in the early phase of differentiation, and an increase of Notch2 and Notch4 receptors in the late phase. Among Notch nuclear target genes, Hey1 expression was significantly higher in OM than control, while Hes5 expression decreased. Osteogenic markers were reduced and Hey1 was significantly inhibited by Notch inhibitors, suggesting a role for Notch through the canonical pathway. In conclusion, Notch pathway might be involved with a dual role in osteogenesis of MG63, through the activation of Notch2, Notch4, and Hey1, inducing osteoblast differentiation and the depression of Notch1, Notch3, and Hes5, maintaining an undifferentiated status. J. Cell. Physiol. 231: 2652-2663, 2016. © 2016 Wiley Periodicals, Inc.

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Retracted: Downregulated microRNA‐488 enhances odontoblast differentiation of human dental pulp stem cells via activation of the p38 MAPK signaling pathway

Zhao

Cheng

et al. 2018

Journal Cellular Physiology

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Human dental pulp stem cells (hDPSCs) are primarily derived from the pulp tissues of permanent third molar teeth. They were widely used in human bone tissue engineering. It was previously indicated that microRNA (miR) expressions are closely associated with hDPSCs development. However, the specific effect of miR-488 on hDPSCs still remains unclear. In this study, we aimed to investigate effects of miR-488 on the differentiation of hDPSCs into odontoblast cells through the p38 mitogen-activated protein kinases (MAPK) signaling pathway by binding to MAPK1. The hDPSCs were isolated and cultured in vitro. Dual-luciferase reporter gene assay was performed to test the relationship between MAPK1 (p38) and miR-488. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expressions of p38 MAPK signaling pathway-related genes (MAPK1, Ras, and Mitogen-activated protein kinase kinase 3/6 [MKK3/6]), along with expressions of dentin Sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteonectin (OCN). ALP staining and alizarin red staining were conducted to detect ALP activity and degree of mineralization. Initially, we found that MAPK1 was the target gene of miR-488. Besides, downregulation of miR-488 was observed to stimulate the p38 MAPK signaling pathway and to increase the messenger RNA and protein expressions of DSPP, ALP, and OCN. Furthermore, ALP activity and formation of a mineralized nodule in hDPSCs were enhanced upon downregulation of miR-488. The aforementioned findings provided evidence supporting that downregulation of miR-488 promotes odontoblastic differentiation of hDPSCs through the p38 MAPK signaling pathway by targeting MAPK1, paving the basis for further study about hDPSCs.

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Human β‐defensins differently affect proliferation, differentiation, and mineralization of osteoblast‐like MG63 cells

Cited by 56 publications

References 44 publications

Human Defensins: Potential Tools for Clinical Applications

Human Defensins: Potential Tools for Clinical Applications

Characterization of Notch Signaling During Osteogenic Differentiation in Human Osteosarcoma Cell Line MG63

Retracted: Downregulated microRNA‐488 enhances odontoblast differentiation of human dental pulp stem cells via activation of the p38 MAPK signaling pathway

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