Expression of collagen type�I and type�II in consecutive stages of human osteoarthritis

Miosge, Nicolai; Hartmann, Michael; Maelicke, Cyrilla; Herken, Rainer

doi:10.1007/s00418-004-0697-6

Cited by 134 publications

(124 citation statements)

References 42 publications

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“…77,78 It is therefore possible that, at some point, the chondrocyte response switches from catabolism to anabolism, and we are capturing this transition with our OAC-AM system. Although Protein production by OACs cocultured with AMs as assessed by western blotting relative to OACs cocultured with NMs.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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“…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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Section: Abstract: Collagen; Gene Expression; Glucose; Human Chondromentioning

confidence: 99%

“…Allied to increased matrix degradation, OA is characterized by a shift in the chondrocyte anabolic activity, so that collagen II synthesis is replaced by increased production of the non-cartilage matrix specific collagen type I. This leads to the formation of a fibrocartilaginous tissue which is biomechanically less effective than articular cartilage [Miosge et al, 2004;Tesche and Miosge, 2005].The activity of MMPs can be negatively regulated at the posttranscriptional level by members of the family of Tissue Inhibitors of MetalloProteases (TIMPs) [Baker et al, 2002]. Among the TIMPs identified in human chondrocytes, TIMP-2 has been reported to be constitutively expressed and therefore suggested to have a role in the maintenance of cartilage integrity in normal conditions, while TIMP-1 and TIMP-3 seem to have a more important role in pathological conditions [Zafarullah et al, 1996;Su et al, 1999].…”

mentioning

confidence: 99%

“…Those genes include the MMPs-1 and -13 due to their major role in cartilage matrix degradation, and collagen type II, TIMP-1 and TIMP-2 as important anabolic and anti-catabolic genes, respectively. Collagen type I was also assessed since it is frequently reported to be increased in OA, representing the inability of OA chondrocytes to promote an adequate cartilage matrix repair response [Miosge et al, 2004]. …”

mentioning

confidence: 99%

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Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

et al. 2011

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Cartilage matrix homeostasis involves a dynamic balance between numerous signals that modulate chondrocyte functions. This study aimed at elucidating the role of the extracellular glucose concentration in modulating anabolic and catabolic gene expression in normal and osteoarthritic (OA) human chondrocytes and its ability to modify the gene expression responses induced by pro-anabolic stimuli, namely Transforming Growth Factor-b (TGF). For this, we analyzed by real time RT-PCR the expression of articular cartilage matrix-specific and nonspecific genes, namely collagen types II and I, respectively. The expression of the matrix metalloproteinases (MMPs)-1 and -13, which plays a major role in cartilage degradation in arthritic conditions, and of their tissue inhibitors (TIMP) was also measured. The results showed that exposure to high glucose (30 mM) increased the mRNA levels of both MMPs in OA chondrocytes, whereas in normal ones only MMP-1 increased. Collagen II mRNA was similarly increased in normal and OA chondrocytes, but the increase lasted longer in the later. Exposure to high glucose for 24 h prevented TGF-induced downregulation of MMP-13 gene expression in normal and OA chondrocytes, while the inhibitory effect of TGF on MMP-1 expression was only partially reduced. Other responses were not significantly modified. In conclusion, exposure of human chondrocytes to high glucose, as occurs in vivo in diabetes mellitus patients and in vitro for the production of engineered cartilage, favors the chondrocyte catabolic program. This may promote articular cartilage degradation, facilitating OA development and/or progression, as well as compromise the quality and consequent in vivo efficacy of tissue engineered cartilage. J. Cell. Biochem. 112: 2813Biochem. 112: -2824Biochem. 112: , 2011. ß 2011 Wiley-Liss, Inc. KEY WORDS: COLLAGEN; GENE EXPRESSION; GLUCOSE; HUMAN CHONDROCYTE; MMP; OSTEOARTHRITIS; TIMPA rticular cartilage is a specialized connective tissue that supports and distributes loads and ensures a near-frictionless motion in joints. These unique properties are due to the structural organization of the main macromolecules that compose the cartilage extracellular matrix, namely collagens and proteoglycans. Chondrocytes, the only cell type present in articular cartilage, are embedded in the extracellular matrix and are responsible for maintaining its homeostasis by ensuring the synthesis and turnover of its components [Martel-Pelletier et al., 2008;Goldring and Marcu, 2009].Cartilage matrix homeostasis involves a dynamic balance between a variety of signals that modulate chondrocyte functions, namely mechanical forces, cytokines and growth factors and cellmatrix interactions, some favoring an anabolic program and others stimulating catabolic responses. Aging and mechanical stress of joints are major risk factors for osteoarthritis (OA), but growing evidence indicates that metabolic factors play an important role in disease development and progression. For instance, a significant positive correlation wa...

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Expression of collagen type�I and type�II in consecutive stages of human osteoarthritis

Cited by 134 publications

References 42 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

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