Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture

Ma, Bin; Leijten, Jeroen; Wu, Lin−Kun; Kip, Michelle M.A.; Blitterswijk, Clemens A. van; Post, Janine N.; Karperien, Marcel

doi:10.1016/j.joca.2013.01.014

Cited by 168 publications

(155 citation statements)

References 16 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…Aggrecan was downregulated after one passage but remained at the same level for the subsequent passages. This dedifferentiation process is well established in chondrocytes [Vondermark et al, 1977;Malda et al, 2003a;Caron et al, 2012;Ma et al, 2013;Meretoja et al, 2014], but only little evidence is available in the literature for meniscal fibrochondrocytes [Gunja and Athanasiou, 2007;Tan et al, , 2011. Decreased collagen II expression and upregulation of collagen I have been reported in other studies using human meniscal fibrochondrocytes [Tan et al, 2011;Croutze et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Redifferentiation of High-Throughput Generated Fibrochondrocyte Micro-Aggregates: Impact of Low Oxygen Tension

Berneel¹,

Philips²,

Declercq³

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

In meniscus tissue engineering strategies, enhancing the matrix quality of the neomeniscal tissue is important. When the differentiated phenotype of fibrochondrocytes is lost, the quality of the matrix becomes compromised. The objective of this study was to produce uniform fibrochondrocyte micro-aggregates with desirable phenotype and tissue homogeneity in large quantities using a simple and reproducible method. Furthermore, we investigated if hypoxia could enhance the matrix quality. Porcine fibrochondrocytes were expanded at 21% oxygen until passage 3 (P3) and a gene expression profile was determined. P3 fibrochondrocytes were cultivated in chondrogenic medium at 5 and 21% oxygen in high-throughput agarose chips containing 2,865 microwells 200 µm in diameter. Evaluation included live/dead staining, histological examination, immunohistochemistry, dimethylmethylene blue assay and real-time reverse transcriptase quantitative polymerase chain reaction of the micro-aggregates. Gene expression analysis showed a drastic decline in collagen II and high expression of collagen I during monolayer culture. After 4 days, uniform and stable micro-aggregates could be produced. The redifferentiation and matrix quality of the hypoxic cultured micro-aggregates were enhanced relative to the normoxic cultures. Sulfated glycosaminoglycan synthesis was significantly higher, and collagen II expression and the collagen II/collagen I ratio were significantly upregulated in the hypoxic cultures. High-throughput production of uniform microtissues holds promise for the generation of larger-scale tissue engineering constructs or optimization of redifferentiation mechanisms for clinical applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Redifferentiation of High-Throughput Generated Fibrochondrocyte Micro-Aggregates: Impact of Low Oxygen Tension

Berneel¹,

Philips²,

Declercq³

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…Over the course of OA development, catabolic factors, including proinflammatory cytokines, are activated, which induces the gradual self-destruction of cartilage coupled with the curb of chondrogenic differentiation (3)(4)(5). Accompanied with this process is the impact of non-cartilage-specific extracellular matrix (ECM) with inferior mechanical properties, which is produced by dedifferentiated chondrocytes and can prevent chondroprogenitors from remodeling cartilage defects through migration (6,7).…”

Section: Introductionmentioning

confidence: 99%

Protocatechuic acid benefits proliferation and phenotypic maintenance of rabbit articular chondrocytes: An in vitro study

Luo

Wei

Liu

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Numerous antioxidants exhibit antiarthritic effects due to their inhibitory effect on inflammatory factors. Certain antioxidants, such as protocatechuic acid (PCA) and its analogs, have been reported to be effective in the treatment of arthritis. However, the effect of PCA on chondro-protection may be alleviated due to the induction of apoptosis, as has been demonstrated in stomatocytes. To clearly determine the effect of PCA on the biological and cellular metabolism of rabbit articular chondrocytes in vitro, examinations of cytotoxicity, proliferation and morphology were performed, in addition to analyses of glycosaminoglycan (GAG) synthesis and the expression of cartilage-specific genes. The results revealed that PCA effectively promoted chondrocyte growth, the synthesis of the extracellular matrix and the mRNA expression of aggrecan, collagen II and Sox9, while downregulating the expression of the collagen I gene, a marker of chondrocyte dedifferentiation. In addition, hypertrophy, which may result in chondrocyte ossification, was not detected in the groups. Among the doses (range, 0.05-0.3 mmol/l) of PCA that promoted the proliferation of chondrocytes, a concentration of 0.125 mmol/l produced the optimum performance. The results indicated that PCA, particularly at a dose of 0.125 mmol/l, accelerated the proliferation of rabbit articular chondrocytes in vitro and maintained their phenotype. This study may provide a basis for further research concerning the treatment of cartilage defects.

show abstract

“…To increase cell number, chondrocytes are expanded ex vivo, but prolonged monolayer culture has proved to induce chondrocyte de-differentiation. Chondrocytes lost their round shape and become flattened fibroblast-like cells with an increased proliferative capacity that is accompanied by changes in gene expression and surface markers including decreased Col II and Aggrecan, and increased levels of Col I and Col X [16]. Thus, strategies to maintain the chondrocyte phenotype in vitro are still needed.…”

Section: Cell Sources and Delivery Methods For Osteochondral Repairmentioning

confidence: 99%

Polymers, scaffolds and bioactive molecules with therapeutic properties in osteochondral pathologies: what’s new?

López‐Ruiz

Jiménez

García

et al. 2016

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

Promising tissue engineering based procedures have emerged as a therapeutic option for the treatment of osteochondral lesions. The development of multilayer scaffolds and the controlled release of bioactive molecules to promote in situ regeneration of both cartilage and bone are some of the latest technologies that intended to improve on the available traditional treatments. To confirm the potential of these novel approaches, long-term evaluation is necessary with special focus on studying the biological and mechanical proprieties of the synthesized tissues.

show abstract

Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture

Abstract: Our study not only improves our knowledge of the intricate signaling network regulating maintenance of chondrocyte phenotype, but also contributes to improved chondrocyte expansion and chondrogenic performance for cell therapy.

Cited by 168 publications

References 16 publications

Redifferentiation of High-Throughput Generated Fibrochondrocyte Micro-Aggregates: Impact of Low Oxygen Tension

Redifferentiation of High-Throughput Generated Fibrochondrocyte Micro-Aggregates: Impact of Low Oxygen Tension

Protocatechuic acid benefits proliferation and phenotypic maintenance of rabbit articular chondrocytes: An in vitro study

Polymers, scaffolds and bioactive molecules with therapeutic properties in osteochondral pathologies: what’s new?

Contact Info

Product

Resources

About