Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage.

Aigner, Thomas; Bertling, Wolf; Stöß, H; Weseloh, G.; Mark, Klaus von der

doi:10.1172/jci116303

Cited by 211 publications

(167 citation statements)

References 38 publications

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“…Current hypotheses to explain the changes in OA chondrocytes include the notion that phenotypic alterations of the cells occur in response to changing signals or matrix composition (10)(11)(12)(13). It is well known that chondrocytes can adopt different phenotypes, including those associated with the growth plate (resting, proliferating, hypertrophic), those associated with the different zones of AC, and the dedifferentiated phenotype observed in monolayer culture (3,7,13,17).…”

Section: Discussionmentioning

confidence: 99%

“…These studies have shown that a major change in the chondrocyte phenotype in OA involves a switch in the types of collagen molecules that are synthesized. Clusters of chondrocytes in OA cartilage have been shown to express types I and III collagens, which are not normally found or found at very low levels in normal AC (10,12,(69)(70)(71).…”

Section: Discussionmentioning

confidence: 99%

“…These changes in the biosynthetic profile of dedifferentiated chondrocytes resemble some of the phenotypic changes displayed by OA chondrocytes, and the matrix they produce is similar to that synthesized by chondroprogenitor cells (7)(8)(9)(10)(11)(12)(13)17,(37)(38)(39)(40). However, the mechanisms responsible for the phenotypic instability of chondrocytes and the regulation of these different chondrocyte-specific phenotypes remain poorly understood.…”

mentioning

confidence: 91%

“…The chondro-cyte response may lead, in certain situations, to longterm changes in the phenotype of the cell, and therefore to an inability to properly repair or maintain the cartilage ECM (4). This is exemplified by the phenotypic changes in the patterns of production or in the temporal or spatial distribution of the synthesis of interstitial collagens, fibroblast-type proteoglycans, and production of ECM proteins associated with fetal development that occur during the development of osteoarthritis (OA), dedifferentiation in culture, or in response to certain types of cartilage injury (6)(7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

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Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

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Objective. To study the changes in patterns of gene expression exhibited by human chondrocytes as they dedifferentiate into fibroblastic cells in culture in order to better understand the mechanisms that control this process and its relationship to the phenotypic changes that occur in chondrocytes during the development of osteoarthritis (OA).Methods. Human fetal epiphyseal chondrocytes (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers (dedifferentiated HFC cultures). Following 11 days of culture under either condition, poly(A؉) RNA was isolated from the two cell populations and subjected to a gene expression analysis using a microarray containing ϳ5,000 known human genes and ϳ3,000 expressed sequence tags (ESTs).Results. A >2-fold difference in the expression of 62 known genes and 6 ESTs was observed between the two cell types. The differences in expression of several of the genes detected by the microarray hybridization were confirmed by Northern analyses. Two transcription factor genes, TWIST and HIF-1␣, and a cellular adhesion protein gene, cadherin 11, were markedly regulated in response to differentiation and dedifferentiation. Expression of these genes was also detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene expression profile of HFCs revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes.Conclusion. Chondrocytes in monolayer become dedifferentiated, acquiring a fibroblast-like appearance and changing their pattern of gene expression from one of expression of chondrocyte-specific genes to one that resembles a fibroblastic or chondroprogenitor-like pattern. Changes in gene expression associated with the process of dedifferentiation of HFCs in vitro were observed in a wide variety of genes, including genes encoding extracellular matrix proteins, transcription factors, and growth factors. At least 3 of the genes that were regulated in response to dedifferentiation were also found to be expressed in adult normal and OA articular cartilage and chondrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

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Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

View full text Add to dashboard Cite

show abstract

“…In these chondrocytes, the expression levels of type IX and type XI procollagens as well as link protein were higher than those in the cells given a control siRNA ( Figure 3C). In dedifferentiating chondrocytes, the expression levels of type I and type III procollagens, which are not very high in normal chondrocytes, have been shown to be induced in parallel with the decline in cartilage matrix gene expression (34)(35)(36)(37)(38). Thus, we expected that the expression of those procollagen genes might be reduced by the suppression of ␣v or ␤5 integrin expression.…”

Section: Determination Of Dominant Integrins In Human Articular Chondmentioning

confidence: 98%

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Fukui¹,

Ikeda²,

Tanaka³

et al. 2011

Arthritis & Rheumatism

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Objective. When cultured in monolayers, articular chondrocytes undergo an obvious phenotypic change. Although the involvement of integrins has been suggested, the exact mechanisms of the change have not been determined. This study was undertaken to clarify the mechanisms underlying the loss of chondrocyte phenotype early after plating.Methods. Primary cultured human articular chondrocytes were used for the experiments. Involvement of respective integrins in the phenotypic change was investigated in RNA interference (RNAi) experiments. A signaling pathway involved in the change was identified in experiments using specific inhibitors and adenoviruses encoding mutated genes involved in the pathway. Adenoviruses carrying mutated GTPases were used to determine the involvement of small GTPases in the process.Results. In monolayer-cultured chondrocytes, suppression of ␣v or ␤5 integrin expression by RNAi inhibited morphologic changes in the cells and increased (or prevented a reduction in) the expression of various cartilage matrix genes. Consistent results were obtained in experiments using a blocking antibody and a synthetic inhibitor of ␣v␤5 integrin. The decrease in cartilage matrix gene expression in chondrocytes after plating was mediated by ERK signaling, which was promoted primarily by ␣v␤5 integrin. In articular chondrocytes, the affinity of ␣v␤5 integrin for ligands was regulated by the small GTPase R-Ras. R-Ras was gradually activated in monolayer-cultured chondrocytes after plating, which caused a gradual decline in cartilage matrix gene expression through enhanced ␣v␤5 integrin activation and the subsequent increase in ERK signaling.Conclusion. Our findings indicate that ␣v␤5 integrin may be involved in the change that occurs in monolayer-cultured chondrocytes after plating.

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Degenerative Changes in the Human Cricoarytenoid Joint

Paulsen

Tillmann²

1998

Arch Otolaryngol Head Neck Surg

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Chondrocyte proliferation next to the joint surface, changed collagen synthesis, and fibrillation of the joint surface indicate degenerative alterations. Such changes are well known in cases of limb diarthroses. The changes may impair gross positional or postural movements of the arytenoid cartilages and reduce the degree and extent of vocal ligament closure. The structural changes may also lead to negative functional consequences during vocal production, such as impaired vocal quality and reduced vocal intensity due to air leakage through incompletely or loosely approximated vocal ligaments.

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Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage.

Cited by 211 publications

References 38 publications

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Degenerative Changes in the Human Cricoarytenoid Joint

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