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A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis

Given the lack of in vitro models faithfully reproducing the osteoarthritis (OA) disease on-set, this work aimed at manufacturing a reliable and predictive in vitro cytokine-based Articular Cartilage (AC) model to study OA progression. Cell spheroids of primary human fetal chondrocytes (FCs) and h-T...

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Autores principales: Scalzone, Annachiara, Cerqueni, Giorgia, Wang, Xiao Nong, Dalgarno, Kenny, Mattioli-Belmonte, Monica, Ferreira-Duarte, Ana M., Gentile, Piergiorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203413/
https://www.ncbi.nlm.nih.gov/pubmed/37229489
http://dx.doi.org/10.3389/fbioe.2023.1167623
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author Scalzone, Annachiara
Cerqueni, Giorgia
Wang, Xiao Nong
Dalgarno, Kenny
Mattioli-Belmonte, Monica
Ferreira-Duarte, Ana M.
Gentile, Piergiorgio
author_facet Scalzone, Annachiara
Cerqueni, Giorgia
Wang, Xiao Nong
Dalgarno, Kenny
Mattioli-Belmonte, Monica
Ferreira-Duarte, Ana M.
Gentile, Piergiorgio
author_sort Scalzone, Annachiara
collection PubMed
description Given the lack of in vitro models faithfully reproducing the osteoarthritis (OA) disease on-set, this work aimed at manufacturing a reliable and predictive in vitro cytokine-based Articular Cartilage (AC) model to study OA progression. Cell spheroids of primary human fetal chondrocytes (FCs) and h-TERT mesenchymal stem cells differentiated chondrocytes (Y201-C) were analysed in terms of growth kinetics, cells proliferation and apoptosis over 10 days of culture, in healthy condition or in presence of cytokines (interleukin-1ß, −6 and TNF-α). Then, the spheroids were assembled into chondrospheres using a bottom-up strategy, to obtain an in vitro cytokines-induced OA model. The resulting chondrospheres were evaluated for gene expression and anabolic ECM proteins. Compared to the healthy environment, the simulated OA environment induced chondrocyte hyperproliferation and apoptotic pathway, decreased expression of anabolic ECM proteins, and diminished biosynthetic activity, resembling features of early-stage OA. These characteristics were observed for both Y201-C and HC at high and low concentrations of cytokines. Both HC and Y201-C demonstrated the suitability for the manufacturing of a scaffold-free in vitro OA model to facilitate studies into OA pathogenesis and therapeutic strategies. Our approach provides a faithful reproduction of early-stage osteoarthritis, demonstrating the ability of obtaining different disease severity by tuning the concentration of OA-related cytokines. Given the advantages in easy access and more reproducible performance, Y201-C may represent a more favourable source of chondrocytes for establishing more standardized protocols to obtain OA models.
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spelling pubmed-102034132023-05-24 A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis Scalzone, Annachiara Cerqueni, Giorgia Wang, Xiao Nong Dalgarno, Kenny Mattioli-Belmonte, Monica Ferreira-Duarte, Ana M. Gentile, Piergiorgio Front Bioeng Biotechnol Bioengineering and Biotechnology Given the lack of in vitro models faithfully reproducing the osteoarthritis (OA) disease on-set, this work aimed at manufacturing a reliable and predictive in vitro cytokine-based Articular Cartilage (AC) model to study OA progression. Cell spheroids of primary human fetal chondrocytes (FCs) and h-TERT mesenchymal stem cells differentiated chondrocytes (Y201-C) were analysed in terms of growth kinetics, cells proliferation and apoptosis over 10 days of culture, in healthy condition or in presence of cytokines (interleukin-1ß, −6 and TNF-α). Then, the spheroids were assembled into chondrospheres using a bottom-up strategy, to obtain an in vitro cytokines-induced OA model. The resulting chondrospheres were evaluated for gene expression and anabolic ECM proteins. Compared to the healthy environment, the simulated OA environment induced chondrocyte hyperproliferation and apoptotic pathway, decreased expression of anabolic ECM proteins, and diminished biosynthetic activity, resembling features of early-stage OA. These characteristics were observed for both Y201-C and HC at high and low concentrations of cytokines. Both HC and Y201-C demonstrated the suitability for the manufacturing of a scaffold-free in vitro OA model to facilitate studies into OA pathogenesis and therapeutic strategies. Our approach provides a faithful reproduction of early-stage osteoarthritis, demonstrating the ability of obtaining different disease severity by tuning the concentration of OA-related cytokines. Given the advantages in easy access and more reproducible performance, Y201-C may represent a more favourable source of chondrocytes for establishing more standardized protocols to obtain OA models. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10203413/ /pubmed/37229489 http://dx.doi.org/10.3389/fbioe.2023.1167623 Text en Copyright © 2023 Scalzone, Cerqueni, Wang, Dalgarno, Mattioli-Belmonte, Ferreira-Duarte and Gentile. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Scalzone, Annachiara
Cerqueni, Giorgia
Wang, Xiao Nong
Dalgarno, Kenny
Mattioli-Belmonte, Monica
Ferreira-Duarte, Ana M.
Gentile, Piergiorgio
A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title_full A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title_fullStr A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title_full_unstemmed A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title_short A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
title_sort cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203413/
https://www.ncbi.nlm.nih.gov/pubmed/37229489
http://dx.doi.org/10.3389/fbioe.2023.1167623
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