Regulation of ADSC Osteoinductive Potential Using Notch Pathway Inhibition and Gene Rescue: A Potential On/Off Switch for Clinical Applications in Bone Formation and Reconstructive Efforts

Lough, Denver M.; Chambers, Christopher B.; Germann, Günter; Bueno, Ruben; Reichensperger, Joel; Swanson, Edward W.; Dyer, Mary A.; Cox, Lisa; Harrison, Carrie; Neumeister, Michael W.

doi:10.1097/prs.0000000000002551

Cited by 22 publications

(10 citation statements)

References 44 publications

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“…These findings imply that endogenous Notch signaling may participate in osteogenic differentiation. Previous reports demonstrated that inhibiting endogenous Notch signaling using a γ-secretase inhibitor reduced the osteogenic differentiation of hADSCs and human umbilical cord mesenchymal stem cells as confirmed by a significant reduction in in vitro mineral deposition 34 , 48 . However, osteogenic medium containing DAPT did not alter ALP enzymatic activity or mineralization by hDPs in the present study.…”

Section: Discussionmentioning

confidence: 80%

“…However, evidence supporting a positive role in osteogenic differentiation is increasing. Notch signaling promoted osteogenic differentiation in hBMSCs, human periodontal ligament stem cells, human adipose stem cells (hADSCs), and SHEDs 8 , 10 , 12 , 48 – 51 . The role of Notch signaling in the odonto/osteogenic differentiation of adult dental cells (SHEDs and periodontal ligament stem cells) was previous reported by a few research groups, including our own.…”

Section: Discussionmentioning

confidence: 99%

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Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells

Manokawinchoke

Nattasit

Thongngam

et al. 2017

Sci Rep

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Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells

Manokawinchoke

Nattasit

Thongngam

et al. 2017

Sci Rep

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“…Similarly, the inhibition of Notch and the associated downregulation of ASC proliferation and osteoinduction has been found to be a useful potential translatable "on/off switch" in the regulation of proliferation, differentiation, and osteogenic potential of ASCs. Additionally, delivery of Notch-1 intracellular domain (NICD), after prior Notch inhibition, restored bone formation [31].…”

Section: Osteogenic Differentiationmentioning

confidence: 99%

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Jankowski

Dompe

Sibiak

et al. 2020

Cells

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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“…A recent study reported that Notch signaling is also directly involved in the osteogenic differentiation of ASCs [ 40 ]. It has been shown that Notch pathway activation improves the osteoinductive ability of ASCs and the formation of the extracellular matrix, whereas the Notch inhibition downregulates the osteogenic commitment of these cells [ 40 ]. These studies suggest that the modulation of Notch signaling could be used to stimulate an osteogenic induction of ASCs.…”

Section: Molecular Mechanisms Responsible For Osteogenic Commitmenmentioning

confidence: 99%

Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications

Paduano¹,

Marrelli

Amantea

et al. 2017

IJMS

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Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts.

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Regulation of ADSC Osteoinductive Potential Using Notch Pathway Inhibition and Gene Rescue: A Potential On/Off Switch for Clinical Applications in Bone Formation and Reconstructive Efforts

Cited by 22 publications

References 44 publications

Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells

Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications

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