Notch signaling has been identified as a critical regulator of cartilage development and homeostasis. Its pivotal role was established by both several joint specific Notch signaling loss of function mouse models and transient or sustained overexpression. NOTCH1 is the most abundantly expressed NOTCH receptors in normal cartilage and its expression increases in osteoarthritis (OA), when chondrocytes exit from their healthy “maturation arrested state” and resume their natural route of proliferation, hypertrophy, and terminal differentiation. The latter are hallmarks of OA that are easily evaluated in vitro in 2-D or 3-D culture models. The aim of our study was to investigate the effect of NOTCH1 knockdown on proliferation (cell count and Picogreen mediated DNA quantification), cell cycle (flow cytometry), hypertrophy (gene and protein expression of key markers such as RUNX2 and MMP-13), and terminal differentiation (viability measured in 3-D cultures by luminescence assay) of human OA chondrocytes. NOTCH1 silencing of OA chondrocytes yielded a healthier phenotype in both 2-D (reduced proliferation) and 3-D with evidence of decreased hypertrophy (reduced expression of RUNX2 and MMP-13) and terminal differentiation (increased viability). This demonstrates that NOTCH1 is a convenient therapeutic target to attenuate OA progression.

Minguzzi M., Panichi V., D'adamo S., Cetrullo S., Cattini L., Flamigni F., et al. (2021). Pleiotropic roles of notch1 signaling in the loss of maturational arrest of human osteoarthritic chondrocytes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(21), 1-22 [10.3390/ijms222112012].

Pleiotropic roles of notch1 signaling in the loss of maturational arrest of human osteoarthritic chondrocytes

Minguzzi M.
Co-primo
;
Panichi V.
Co-primo
;
D'adamo S.;Cetrullo S.;Flamigni F.;Mariani E.;
2021

Abstract

Notch signaling has been identified as a critical regulator of cartilage development and homeostasis. Its pivotal role was established by both several joint specific Notch signaling loss of function mouse models and transient or sustained overexpression. NOTCH1 is the most abundantly expressed NOTCH receptors in normal cartilage and its expression increases in osteoarthritis (OA), when chondrocytes exit from their healthy “maturation arrested state” and resume their natural route of proliferation, hypertrophy, and terminal differentiation. The latter are hallmarks of OA that are easily evaluated in vitro in 2-D or 3-D culture models. The aim of our study was to investigate the effect of NOTCH1 knockdown on proliferation (cell count and Picogreen mediated DNA quantification), cell cycle (flow cytometry), hypertrophy (gene and protein expression of key markers such as RUNX2 and MMP-13), and terminal differentiation (viability measured in 3-D cultures by luminescence assay) of human OA chondrocytes. NOTCH1 silencing of OA chondrocytes yielded a healthier phenotype in both 2-D (reduced proliferation) and 3-D with evidence of decreased hypertrophy (reduced expression of RUNX2 and MMP-13) and terminal differentiation (increased viability). This demonstrates that NOTCH1 is a convenient therapeutic target to attenuate OA progression.
2021
Minguzzi M., Panichi V., D'adamo S., Cetrullo S., Cattini L., Flamigni F., et al. (2021). Pleiotropic roles of notch1 signaling in the loss of maturational arrest of human osteoarthritic chondrocytes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(21), 1-22 [10.3390/ijms222112012].
Minguzzi M.; Panichi V.; D'adamo S.; Cetrullo S.; Cattini L.; Flamigni F.; Mariani E.; Borzi R.M.
File in questo prodotto:
File Dimensione Formato  
ijms-22-12012.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 4.72 MB
Formato Adobe PDF
4.72 MB Adobe PDF Visualizza/Apri
ijms-1320137-supplementary.pdf

accesso aperto

Descrizione: Supplementary file
Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Altra tipologia di licenza compatibile con Open Access
Dimensione 3.39 MB
Formato Adobe PDF
3.39 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/839696
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact