Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints

Martin, Ivan; Jakob, Marcel; Schäfer, Dirk; Dick, W.; Spagnoli, Giulio C.; Heberer, Michael

doi:10.1053/joca.2000.0366

Cited by 321 publications

(229 citation statements)

References 20 publications

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“…Conflicting data exist about the expression of collagen type I in osteoarthritic cartilage: whereas some reported strong expression of collagen type I in osteoarthritic cartilage using a similar technique as we in our study (290xCAPDH [20]), we were previously not able to show significant collagen type 1 expression by in situ hybridization [l]. However, in situ hybridization is very limited in terms of detection sensitivity.…”

Section: Discussioncontrasting

confidence: 56%

Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytes

Gebhard

Gehrsitz

Bau

et al. 2003

Journal Orthopaedic Research

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Many studies have shown increased anabolic activity in osteoarthritic cartilage and have suggested changes in the cellular phenotypes of articular chondrocytes. Most of these studies relied on non-quantitative technologies, which did not allow the estimation of the relative importance of the different differentiation phenomena. In the present study, we developed and used quantitative PCR assays for collagen types I, II(total), HA, 111, and X as marker genes indicating cellular synthetic activity (collagen type 11) as well as differentiation pattern of chondrocytes (collagen types I, IIA, 111, and X) and quantified these genes in normal, early degenerative, and late stage osteoarthritic cartilage in parallel.At first sight, our results confirmed previously published data showing hardly any expression of collagen genes in normal and significantly enhanced expression in osteoarthritic cartilage. This included collagen types 11, 111, and IIA, but also collagen types I(ct1) and X. However, if one considers the ratios of the various markers of chondrocytic differentiation in comparison to collagen type 11, the main synthetic product of differentiated chondrocytes, no shift in the cellular phenotype was detectable. In fact, expression ratios remained constant or were even decreased in osteoarthritic cartilage.Our results confirm that normal adult human articular chondrocytes display hardly any expression activity of the collagen types investigated, whereas osteoarthritic chondrocytes show very increased synthetic activity. The largely unchanged ratios of collagen subtypes investigated indicate that no general shift in the cellular phenotype does occur in osteoarthritic cartilage as suggested by previous investigations.

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Section: Discussioncontrasting

confidence: 56%

Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytes

Gebhard

Gehrsitz

Bau

et al. 2003

Journal Orthopaedic Research

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“…Collagen I is not normally found in articular cartilage and its expression increases in OA and in association with chondrocyte dedifferentiation, a process that involves several alterations of chondrocyte gene expression and morphology and leads to the formation of fibrocartilage (Martin et al, 2001). Therefore, even though it did not increase the specific anabolic responses of human chondrocytes, myrcene may be effective in preventing chondrocyte dedifferentiation associated with increased collagen I expression, while decreasing inflammatory and catabolic processes directly involved in cartilage destruction.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

Rufino

Ribeiro

Sousa

et al. 2015

European Journal of Pharmacology

175

101

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a b s t r a c tOsteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpenes, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti-catabolic and pro-anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1β-induced nitric oxide production (IC 50 ¼ 37.3 μg/ml and 85.3 mg/ml, respectively), but E-caryophyllene was inactive.Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and -3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1β-treated cells. None of the compounds tested was able to increase the expression of cartilage matrix-specific genes (collagen II and aggrecan), but both compounds prevented the increased expression of the non-cartilage specific, collagen I, induced by IL-1β. These data show that myrcene has significant anti-inflammatory and anti-catabolic effects in human chondrocytes and, thus, its ability to halt or, at least, slow down cartilage destruction and osteoarthritis progression warrants further investigation.

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“…Nonetheless, this difference did not reach statistical significance, reflecting a great variability between individuals in each group that only much larger cohorts would minimize. The Col II/Col I ratio has been defined as a chondrocyte differentiation index and used to characterize normal and OA cartilage and the differentiation state of monolayer chondrocyte cultures, where lower ratios correspond to a less differentiated phenotype [Martin et al, 2001;Marlovits et al, 2004]. Even so, since we could not obtain age-matched normal and OA cartilage samples and given the relatively large age range in each group, the possibility that the differences observed are age-related cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

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...

show abstract

Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints

Cited by 321 publications

References 20 publications

Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytes

Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytes

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

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

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