Dedifferentiation alters chondrocyte nuclear mechanics during in vitro culture and expansion.

Autor:	Ghosh S; Department of Mechanical Engineering, Colorado State University, Fort Collins, CO; School of Biomedical Engineering, Colorado State University, Fort Collins, CO; Translational Medicine Institute, Colorado State University, Fort Collins, CO. Electronic address: soham.ghosh@colostate.edu., Scott AK; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO., Seelbinder B; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO., Barthold JE; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO., Martin BMS; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO., Kaonis S; School of Biomedical Engineering, Colorado State University, Fort Collins, CO; Translational Medicine Institute, Colorado State University, Fort Collins, CO., Schneider SE; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO., Henderson JT; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN., Neu CP; Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO; Biomedical Engineering Program, University of Colorado Boulder, Boulder, CO; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2022 Jan 04; Vol. 121 (1), pp. 131-141. Date of Electronic Publication: 2021 Nov 17.
DOI:	10.1016/j.bpj.2021.11.018
Abstrakt:	The biophysical features of a cell can provide global insights into diverse molecular changes, especially in processes like the dedifferentiation of chondrocytes. Key biophysical markers of chondrocyte dedifferentiation include flattened cellular morphology and increased stress-fiber formation. During cartilage regeneration procedures, dedifferentiation of chondrocytes during in vitro expansion presents a critical limitation to the successful repair of cartilage tissue. Our study investigates how biophysical changes of chondrocytes during dedifferentiation influence the nuclear mechanics and gene expression of structural proteins located at the nuclear envelope. Through an experimental model of cell stretching and a detailed spatial intranuclear strain quantification, we identified that strain is amplified and the distribution of strain within the chromatin is altered under tensile loading in the dedifferentiated state. Further, using a confocal microscopy image-based finite element model and simulation of cell stretching, we found that the cell shape is the primary determinant of the strain amplification inside the chondrocyte nucleus in the dedifferentiated state. Additionally, we found that nuclear envelope proteins have lower gene expression in the dedifferentiated state. This study highlights the role of cell shape in nuclear mechanics and lays the groundwork to design biophysical strategies for the maintenance and enhancement of the chondrocyte phenotype during cell expansion with a goal of successful cartilage tissue engineering. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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