Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels
Abstract
The differentiated phenotype of rabbit articular chondrocytes consists primarily of type II collagen and cartilage-specific proteoglycan. During serial monolayer culture this phenotype is lost and replaced by a complex collagen phenotype consisting predominately of type I collagen and a low level of proteoglycan synthesis. Such dedifferentiated chondrocytes reexpress the differentiated phenotype during suspension culture in firm gels of 0.5% low Tm agarose. Approximately 80% of the cells survive this transition from the flattened morphology of anchorage-dependent culture to the spherical morphology of anchorage-independent culture and then deposit characteristic proteoglycan matrix domains. The rates of proteoglycan and collagen synthesis return to those of primary chondrocytes. Using SDS-polyacrylamide gel electrophoresis of intact collagen chains and two-dimensional cyanogen bromide peptide mapping, we demonstrated a complete return to the differentiated collagen phenotype. These results emphasize the primary role of cell shape in the modulation of the chondrocyte phenotype and demonstrate a reversible system for the study of gene expression.
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Cells cultured in three-dimensional arrangements exhibit notable differences in morphology and physiology compared to cells grown in monolayers.
“cells cultured in three-dimensional arrangements exhibit notable differences in morphology and physiology compared to cells grown in monolayers [188,189,190].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [188]
Cells in the 3D culture environment differ morphologically and physiologically from cells in the 2D culture environment.
“In fact, research has found that cells in the 3D culture environment differ morphologically and physiologically from cells in the 2D culture environment. 8-10”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [9]
Cells in a 3D culture environment differ in gene, protein, and cell receptor expression from 2D-cultured cells.
“In addition to the previously mentioned differences in physical and physiological properties, researchers have also found that cells in a 3D culture environment differ in gene, protein, and cell receptor expression from 2D-cultured cells. 8-10”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [9]
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- Authors
- Benya, P. D., & Shaffer, J. D.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Benya, Paul D.
- ORCID
- Benya, Paul D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1982-08
- Volume
- 30
- Issue
- 1
- Pages
- 215-224
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2050273631
- Cited by
- 2,284
- References
- 47
- Citations by year
- 2026: 19 · 2025: 18 · 2024: 32 · 2023: 44 · 2022: 39 · 2021: 40 · 2020: 61 · 2019: 44 · 2018: 61 · 2017: 78 · 2016: 65 · 2015: 64 · 2014: 85 · 2013: 74 · 2012: 96
- FWCI
- 22.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- chondrocyte dedifferentiation, type II collagen, type I collagen, proteoglycan synthesis, suspension culture, cell shape, cartilage, gene expression regulation
- MeSH terms
- Animals, Calcium, Cartilage, Articular, Cell Differentiation, Cells, Cultured, Collagen, DNA, Gels, Peptides, Proteoglycans, Rabbits, Sepharose, Protein Biosynthesis
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