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Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes.
Scott, Adrienne K; Gallagher, Katie M; Schneider, Stephanie E; Kurse, Abhijit; Neu, Corey P.
Afiliación
  • Scott AK; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado, USA.
  • Gallagher KM; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado, USA.
  • Schneider SE; Biomedical Engineering Program, University of Colorado Boulder, Boulder, Colorado, USA.
  • Kurse A; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado, USA.
  • Neu CP; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado, USA.
Tissue Eng Part A ; 30(9-10): 415-425, 2024 May.
Article en En | MEDLINE | ID: mdl-38323554
ABSTRACT
Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure, such as matrix-induced autologous chondrocyte implantation. Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to (1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a three-dimensional (3D) culture; and (2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0 population doublings, 8 population doublings, and 16 population doublings (PD16) in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a 3D hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for PD16 and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded bovine chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Condrocitos / Condrogénesis / Epigénesis Genética Límite: Animals Idioma: En Revista: Tissue Eng Part A Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Condrocitos / Condrogénesis / Epigénesis Genética Límite: Animals Idioma: En Revista: Tissue Eng Part A Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos