TY - JOUR

T1 - Dose-dependent mechanism of Notch action in promoting osteogenic differentiation of mesenchymal stem cells

AU - Semenova, Daria

AU - Bogdanova, Maria

AU - Kostina, Aleksandra

AU - Golovkin, Alexey

AU - Kostareva, Anna

AU - Malashicheva, Anna

N1 - Semenova, D., Bogdanova, M., Kostina, A. et al. Cell Tissue Res (2020) 379: 169. https://doi.org/10.1007/s00441-019-03130-7

PY - 2020/1

Y1 - 2020/1

N2 - Osteogenic differentiation is a tightly regulated process realized by progenitor cell osteoblasts. Notch signaling pathway plays a critical role in skeletal development and bone remodeling. Controversial data exist regarding the role of Notch activation in promoting or preventing osteogenic differentiation. This study aims to investigate the effect of several Notch components and their dosage on osteogenic differentiation of mesenchymal stem cells of adipose tissue. Osteogenic differentiation was induced in the presence of either of Notch components (NICD, Jag1, Dll1, Dll4) dosed by lentiviral transduction. We show that osteogenic differentiation was increased by NICD and Jag1 transduction in a dose-dependent manner; however, a high dosage of both NICD and Jag1 decreased the efficiency of osteogenic differentiation. NICD dose-dependently increased activity of the CSL luciferase reporter but a high dosage of NICD caused a decrease in the activity of the reporter. A high dosage of both Notch components NICD and Jag1 induced apoptosis. In co-culture experiments where only half of the cells were transduced with either NICD or Jag1, only NICD increased osteogenic differentiation according to the dosage, while Jag1-transduced cells differentiated almost equally independently on dosage. In conclusion, activation of Notch promotes osteogenic differentiation in a tissue-specific dose-dependent manner; both NICD and Jag1 are able to increase osteogenic potential but at moderate doses only and a high dosage of Notch activation is detrimental to osteogenic differentiation. This result might be especially important when considering possibilities of using Notch activation to promote osteogenesis in clinical applications to bone repair.

AB - Osteogenic differentiation is a tightly regulated process realized by progenitor cell osteoblasts. Notch signaling pathway plays a critical role in skeletal development and bone remodeling. Controversial data exist regarding the role of Notch activation in promoting or preventing osteogenic differentiation. This study aims to investigate the effect of several Notch components and their dosage on osteogenic differentiation of mesenchymal stem cells of adipose tissue. Osteogenic differentiation was induced in the presence of either of Notch components (NICD, Jag1, Dll1, Dll4) dosed by lentiviral transduction. We show that osteogenic differentiation was increased by NICD and Jag1 transduction in a dose-dependent manner; however, a high dosage of both NICD and Jag1 decreased the efficiency of osteogenic differentiation. NICD dose-dependently increased activity of the CSL luciferase reporter but a high dosage of NICD caused a decrease in the activity of the reporter. A high dosage of both Notch components NICD and Jag1 induced apoptosis. In co-culture experiments where only half of the cells were transduced with either NICD or Jag1, only NICD increased osteogenic differentiation according to the dosage, while Jag1-transduced cells differentiated almost equally independently on dosage. In conclusion, activation of Notch promotes osteogenic differentiation in a tissue-specific dose-dependent manner; both NICD and Jag1 are able to increase osteogenic potential but at moderate doses only and a high dosage of Notch activation is detrimental to osteogenic differentiation. This result might be especially important when considering possibilities of using Notch activation to promote osteogenesis in clinical applications to bone repair.

KW - Mesenchymal stem cells

KW - Notch

KW - Osteogenic differentiation

KW - ACTIVATION

KW - GENE

KW - SIGNALING PATHWAY

KW - EXPANSION

KW - BONE

KW - STROMAL CELLS

KW - EXPRESSION

KW - PRECURSORS

KW - INSIGHTS

KW - osteogenic differentiation

KW - mesenchymal stem cells

KW - notch

UR - http://www.scopus.com/inward/record.url?scp=85075662777&partnerID=8YFLogxK

UR - http://link.springer.com/10.1007/s00441-019-03130-7

UR - http://www.mendeley.com/research/dosedependent-mechanism-notch-action-promoting-osteogenic-differentiation-mesenchymal-stem-cells

U2 - 10.1007/s00441-019-03130-7

DO - 10.1007/s00441-019-03130-7

M3 - Article

AN - SCOPUS:85075662777

VL - 379

SP - 169

EP - 179

JO - Cell and Tissue Research

JF - Cell and Tissue Research

SN - 0302-766X

IS - 1

ER -