The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes

The preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results high...

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Main Authors: Carlos Martinez-Armenta, Carlos Suarez-Ahedo, Anell Olivos-Meza, María C. Camacho-Rea, Laura E. Martínez-Gómez, Guadalupe Elizabeth Jimenez-Gutierrez, Gabriela A. Martínez-Nava, Luis E. Gomez-Quiroz, Carlos Pineda, Alberto López-Reyes
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/16/2553
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author Carlos Martinez-Armenta
Carlos Suarez-Ahedo
Anell Olivos-Meza
María C. Camacho-Rea
Laura E. Martínez-Gómez
Guadalupe Elizabeth Jimenez-Gutierrez
Gabriela A. Martínez-Nava
Luis E. Gomez-Quiroz
Carlos Pineda
Alberto López-Reyes
author_facet Carlos Martinez-Armenta
Carlos Suarez-Ahedo
Anell Olivos-Meza
María C. Camacho-Rea
Laura E. Martínez-Gómez
Guadalupe Elizabeth Jimenez-Gutierrez
Gabriela A. Martínez-Nava
Luis E. Gomez-Quiroz
Carlos Pineda
Alberto López-Reyes
author_sort Carlos Martinez-Armenta
collection DOAJ
description The preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results highlight the chondrogenic potential of cultured human articular chondrocytes in a 3D system combined with hypoxia independently of the cartilage source. After 14 days of culture, we developed spheroids with homogenous diameter and shape from hyaline cartilage donors. Spheroids generated in hypoxia showed a significantly increased glycosaminoglycans synthesis and up-regulated the expression of <i>SOX9</i>, <i>ACAN</i>, <i>COL2A1</i>, <i>COMP</i>, and <i>SNAI1</i> compared to those obtained under normoxic conditions. Therefore, we conclude that spheroids developed under hypoxic conditions modulate the expression of chondrogenesis-related genes and native tissue features better than 2D cultures. Thus, this scaffold-free 3D culture system represents a novel in vitro model that can be used for cartilage biology research.
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spelling doaj.art-90ddb9c2196940489a3524c528053a1e2023-11-30T21:06:50ZengMDPI AGCells2073-44092022-08-011116255310.3390/cells11162553The Critical Role of Hypoxia in the Re-Differentiation of Human Articular ChondrocytesCarlos Martinez-Armenta0Carlos Suarez-Ahedo1Anell Olivos-Meza2María C. Camacho-Rea3Laura E. Martínez-Gómez4Guadalupe Elizabeth Jimenez-Gutierrez5Gabriela A. Martínez-Nava6Luis E. Gomez-Quiroz7Carlos Pineda8Alberto López-Reyes9Graduate Program in Experimental Biology, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoDepartamento de Reconstrucción Articular, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoServicio de Medicina del Deporte y Ortopedia, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoDepartamento de Nutrición Animal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Secretaria de Salud, Mexico City 14080, MexicoLaboratorio de Gerociencias, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoLaboratorio de Gerociencias, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoLaboratorio de Gerociencias, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoLaboratorio de Medicina Experimental y Carcinogénesis, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoDirección General, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoLaboratorio de Gerociencias, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibara”, Mexico City 14389, MexicoThe preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results highlight the chondrogenic potential of cultured human articular chondrocytes in a 3D system combined with hypoxia independently of the cartilage source. After 14 days of culture, we developed spheroids with homogenous diameter and shape from hyaline cartilage donors. Spheroids generated in hypoxia showed a significantly increased glycosaminoglycans synthesis and up-regulated the expression of <i>SOX9</i>, <i>ACAN</i>, <i>COL2A1</i>, <i>COMP</i>, and <i>SNAI1</i> compared to those obtained under normoxic conditions. Therefore, we conclude that spheroids developed under hypoxic conditions modulate the expression of chondrogenesis-related genes and native tissue features better than 2D cultures. Thus, this scaffold-free 3D culture system represents a novel in vitro model that can be used for cartilage biology research.https://www.mdpi.com/2073-4409/11/16/2553chondrocytehypoxiacartilagere-differentiation3D cell culture
spellingShingle Carlos Martinez-Armenta
Carlos Suarez-Ahedo
Anell Olivos-Meza
María C. Camacho-Rea
Laura E. Martínez-Gómez
Guadalupe Elizabeth Jimenez-Gutierrez
Gabriela A. Martínez-Nava
Luis E. Gomez-Quiroz
Carlos Pineda
Alberto López-Reyes
The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
Cells
chondrocyte
hypoxia
cartilage
re-differentiation
3D cell culture
title The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
title_full The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
title_fullStr The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
title_full_unstemmed The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
title_short The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes
title_sort critical role of hypoxia in the re differentiation of human articular chondrocytes
topic chondrocyte
hypoxia
cartilage
re-differentiation
3D cell culture
url https://www.mdpi.com/2073-4409/11/16/2553
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