Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes

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...

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Autores principales:	Manuela Minguzzi, Veronica Panichi, Stefania D’Adamo, Silvia Cetrullo, Luca Cattini, Flavio Flamigni, Erminia Mariani, Rosa Maria Borzì
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	osteoarthritis chondrocytes hypertrophy remodeling angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5a358195dec846698abc8316bc227970
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spelling	oai:doaj.org-article:5a358195dec846698abc8316bc2279702021-11-11T17:25:39ZPleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes10.3390/ijms2221120121422-00671661-6596https://doaj.org/article/5a358195dec846698abc8316bc2279702021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12012https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Notch 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.Manuela MinguzziVeronica PanichiStefania D’AdamoSilvia CetrulloLuca CattiniFlavio FlamigniErminia MarianiRosa Maria BorzìMDPI AGarticleosteoarthritischondrocyteshypertrophyremodelingangiogenesisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12012, p 12012 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoarthritis chondrocytes hypertrophy remodeling angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	osteoarthritis chondrocytes hypertrophy remodeling angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999 Manuela Minguzzi Veronica Panichi Stefania D’Adamo Silvia Cetrullo Luca Cattini Flavio Flamigni Erminia Mariani Rosa Maria Borzì Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
description	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.
format	article
author	Manuela Minguzzi Veronica Panichi Stefania D’Adamo Silvia Cetrullo Luca Cattini Flavio Flamigni Erminia Mariani Rosa Maria Borzì
author_facet	Manuela Minguzzi Veronica Panichi Stefania D’Adamo Silvia Cetrullo Luca Cattini Flavio Flamigni Erminia Mariani Rosa Maria Borzì
author_sort	Manuela Minguzzi
title	Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
title_short	Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
title_full	Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
title_fullStr	Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
title_full_unstemmed	Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes
title_sort	pleiotropic roles of notch1 signaling in the loss of maturational arrest of human osteoarthritic chondrocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5a358195dec846698abc8316bc227970
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Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes

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