The Notch1 signaling pathway directly modulates the human RANKL-induced osteoclastogenesis Article Swipe
Costanzo Padovano
,
Salvatore Daniele Bianco
,
Francesca Sansico
,
Elisabetta De Santis
,
Francesco Tamiro
,
Mattia Colucci
,
Beatrice Totti
,
Serena Di Iasio
,
Gaja Bruno
,
Patrizio Panelli
,
Giuseppe Miscio
,
Tommaso Mazza
,
Vincenzo Giambra
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-48615-2
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-48615-2
Notch signaling is an evolutionary conserved pathway with a key role in tissue homeostasis, differentiation and proliferation. It was reported that Notch1 receptor negatively regulates mouse osteoclast development and formation by inhibiting the expression of macrophage colony-stimulating factor in mesenchymal cells. Nonetheless, the involvement of Notch1 pathway in the generation of human osteoclasts is still controversial. Here, we report that the constitutive activation of Notch1 signaling induced a differentiation block in human mononuclear CD14 + cells directly isolated from peripheral blood mononuclear cells (PBMCs) upon in vitro stimulation to osteoclasts. Additionally, using a combined approach of single-cell RNA sequencing (scRNA-Seq) simultaneously with a panel of 31 oligo-conjugated antibodies against cell surface markers (AbSeq assay) as well as unsupervised learning methods, we detected four different cell stages of human RANKL-induced osteoclastogenesis after 5 days in which Notch1 signaling enforces the cell expansion of specific subsets. These cell populations were characterized by distinct gene expression and immunophenotypic profiles and active Notch1, JAK/STAT and WNT signaling pathways. Furthermore, cell–cell communication analyses revealed extrinsic modulators of osteoclast progenitors including the IL7/IL7R and WNT5a/RYK axes. Interestingly, we also report that Interleukin-7 receptor (IL7R) was a downstream effector of Notch1 pathway and that Notch1 and IL7R interplay promoted cell expansion of human RANKL-induced osteoclast progenitors. Taken together, these findings underline a novel cell pattern of human osteoclastogenesis, outlining the key role of Notch1 and IL-7R signaling pathways.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-023-48615-2
- https://www.nature.com/articles/s41598-023-48615-2.pdf
- OA Status
- gold
- Cited By
- 7
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4389224421
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Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4389224421Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-023-48615-2Digital Object Identifier
- Title
-
The Notch1 signaling pathway directly modulates the human RANKL-induced osteoclastogenesisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-12-01Full publication date if available
- Authors
-
Costanzo Padovano, Salvatore Daniele Bianco, Francesca Sansico, Elisabetta De Santis, Francesco Tamiro, Mattia Colucci, Beatrice Totti, Serena Di Iasio, Gaja Bruno, Patrizio Panelli, Giuseppe Miscio, Tommaso Mazza, Vincenzo GiambraList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-023-48615-2Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-023-48615-2.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-023-48615-2.pdfDirect OA link when available
- Concepts
-
Cell biology, RANKL, Wnt signaling pathway, Signal transduction, Osteoclast, Biology, Notch signaling pathway, Progenitor cell, Cellular differentiation, Cell, Receptor, Stem cell, Activator (genetics), Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 1Per-year citation counts (last 5 years)
- References (count)
-
58Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.source.host_organization_lineage_names | Nature Portfolio, Springer Nature |
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| primary_location.pdf_url | https://www.nature.com/articles/s41598-023-48615-2.pdf |
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| publication_date | 2023-12-01 |
| publication_year | 2023 |
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