Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cartilage tissue engineering relies on in vitro expansion of primary chondrocytes. Monolayer is the chosen culture model for chondrocyte expansion because in this system the proliferative capacity of chondrocytes is substantially higher compared to non-adherent systems. However, human articular chondrocytes (HACs) cultured as monolayers undergo changes in phenotype and gene expression known as "dedifferentiation." To gain a better understanding of the cellular mechanisms involved in the dedifferentiation process, our research focused on the characterization of the surface molecule phenotype of HACs in monolayer culture. Adult HACs were isolated by enzymatic digestion of cartilage samples obtained post-mortem. HACs cultured in monolayer for different time periods were analyzed by flow cytometry for the expression of cell surface markers with a panel of 52 antibodies. Our results show that HACs express surface molecules belonging to different categories: integrins and other adhesion molecules (CD49a, CD49b, CD49c, CD49e, CD49f, CD51/61, CD54, CD106, CD166, CD58, CD44), tetraspanins (CD9, CD63, CD81, CD82, CD151), receptors (CD105, CD119, CD130, CD140a, CD221, CD95, CD120a, CD71, CD14), ectoenzymes (CD10, CD26), and other surface molecules (CD90, CD99). Moreover, differential expression of certain markers in monolayer culture was identified. Up-regulation of markers on HACs regarded as distinctive for mesenchymal stem cells (CD10, CD90, CD105, CD166) during monolayer culture suggested that dedifferentiation leads to reversion to a primitive phenotype. This study contributes to the definition of HAC phenotype, and provides new potential markers to characterize chondrocyte differentiation stage in the context of tissue engineering applications.
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PMID:Immunophenotypic analysis of human articular chondrocytes: changes in surface markers associated with cell expansion in monolayer culture. 1538 73

In this study, a time-course comparison of human articular chondrocytes (HAC) and bone marrow-derived mesenchymal stem cells (MSC) immunophenotype was performed in order to determine similarities/differences between both cell types during monolayer culture, and to identify HAC surface markers indicative of dedifferentiation. Our results show that dedifferentiated HAC can be distinguished from MSC by combining CD14, CD90, and CD105 expression, with dedifferentiated HAC being CD14+/CD90bright/CD105dim and MSC being CD14-/CD90dim/CD105bright. Surface markers on MSC showed little variation during the culture, whereas HAC showed upregulation of CD90, CD166, CD49c, CD44, CD10, CD26, CD49e, CD151, CD51/61, and CD81, and downregulation of CD49a, CD54, and CD14. Thus, dedifferentiated HAC appear as a bona fide cell population rather than a small population of MSC amplified during monolayer culture. While most of the HAC surface markers showed major changes at the beginning of the culture period (Passage 1-2), CD26 was upregulated and CD49a downregulated at later stages of the culture (Passage 3-4). To correlate changes in HAC surface markers with changes in extracellular matrix gene expression during monolayer culture, CD14 and CD90 mRNA levels were combined into a new differentiation index and compared with the established differentiation indices based on the ratios of mRNA levels of collagen type II to I (COL2/COL1) and of aggrecan to versican (AGG/VER). A correlation of CD14/CD90 ratio at the mRNA and protein level with the AGG/VER ratio during HAC dedifferentiation in monolayer culture validated CD14/CD90 as a new membrane and mRNA based HAC differentiation index.
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PMID:Immunophenotypic changes of human articular chondrocytes during monolayer culture reflect bona fide dedifferentiation rather than amplification of progenitor cells. 1755 82

We undertook this study to characterize changes in the proliferative capacities, chondrogenic phenotypes, and gene expression profiles of human synovium-derived progenitor cells from osteoarthritic patients during in vitro expansion. Cells isolated from osteoarthritic synovia were cultured, and growth rates during serial passages were evaluated. Surface molecule expressions were determined by flow cytometry and cytogenetic analyses were performed. After chondrogenic differentiation in cell pellets, we evaluated type II collagen and glycosaminoglycan (GAG) synthesis. To assess whether the in vitro expansion of synovium-derived cells affects gene expression, we performed microarray analyses on cells at passage 0, 1, 2, 4, 6, and 8. Synovium-derived cells were rapidly expanded in vitro through passage 8 (about 130 days), and after passage 6, the proliferation rates decreased slightly with a wide range of individual variations. The expressions of CD166, CD49a, and CD106 decreased, whereas those of CD10, CD29, CD44, CD73, CD90, and CD105 showed no significant change. Karyotype analysis revealed no evidence of chromosome abnormalities. The staining of type II collagen and GAG in differentiated cell pellets showed rapid weakening. Genome-wide microarray analysis showed that synovium-derived cells from late passages over-expressed genes associated with cell cycle prolongation and cell aging, and less-expressed genes associated with cell growth stimulation. The in vitro expansion of synovium-derived cells was accompanied with decreased proliferative capacity and the chondrogenic phenotype, which might be modulated by change in gene expression patterns.
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PMID:Changes in chondrogenic phenotype and gene expression profiles associated with the in vitro expansion of human synovium-derived cells. 2022 85