Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype

Yagi, Ryoji; McBurney, Denise L.; Laverty, David; Weiner, Scott D.; Horton, Walter E.

doi:10.1016/j.orthres.2004.12.016

Cited by 84 publications

(81 citation statements)

References 54 publications

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“…We assessed the microarray data for genes that in previous studies were shown to be differentially expressed in intact versus damaged regions of OA cartilage from the same joint or in normal versus OA cartilage from different patients (4)(5)(6)(7)14,(34)(35)(36)(37)(38). The name and symbol of the reported genes are shown in Table 3.…”

Section: Results Of Real-time Quantitative Pcr Of Selected 8 Genesmentioning

confidence: 99%

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Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Sato

Konomi

Yamasaki

et al. 2006

Arthritis & Rheumatism

154

130

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Objective. To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.Methods. We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real-time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data.Results. About 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed >2-fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n ‫؍‬ 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound-healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real-time quantitative PCR data with the previously reported data support the validity of our microarray data.Conclusion. Differences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA.

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Section: Results Of Real-time Quantitative Pcr Of Selected 8 Genesmentioning

confidence: 99%

“…Therefore, changes in the gene expression patterns of chondrocytes in response to various exogenous stimuli could affect the integrity of articular cartilage. Based on this concept, many groups of investigators have reported that gene expression in certain molecules differ from region to region within a single OA joint (4)(5)(6)(7).…”

mentioning

confidence: 99%

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Sato

Konomi

Yamasaki

et al. 2006

Arthritis & Rheumatism

154

130

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“…Scoring criteria were based on Yagi et al (2005). Statistics were calculated using the Mann-Whitney independent samples test, with p value less than 0.05 considered significant.…”

Section: Scoring Of Cartilage Samplesmentioning

confidence: 99%

“…Using our previously published model system utilizing intra-joint comparisons to represent minimal and advanced stages in the morphological progression of OA (Yagi et al 2005), we examined specific cellular and matrix changes associated with human OA. Our results demonstrate an upregulation of grp78 associated with human OA, suggesting that chondrocytes are experiencing altered ER function.…”

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confidence: 99%

Advanced Osteoarthritis in Humans Is Associated With Altered Collagen VI Expression and Upregulation of ER-stress Markers Grp78 and Bag-1

Nugent

Speicher

Gradisar

et al. 2009

J Histochem Cytochem.

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; and Summa Health Systems, Akron, Ohio (IG) S U M M A R Y To test the hypothesis that a perturbation of endoplasmic reticulum (ER) function is involved in the pathogenesis of osteoarthritis (OA), articular cartilage was isolated from non-OA patients secondary to resection of osteo-or chondrosarcomas. Intra-joint samples of minimal and advanced osteoarthritic cartilage were isolated from patients undergoing total knee arthroplasty and scored for disease severity. Glucose-regulated protein-78 (grp78) and bcl-2-associated athanogene-1 (bag-1) were detected via immunofluorescence as markers of non-homeostatic ER function. Additionally, the expression of type VI collagen and its integrin receptor, NG2, was determined to examine cartilage matrix health and turnover. There was an upregulation of grp78 in advanced OA, and variable expression in minimal OA. Non-OA cartilage was consistently grp78 negative. The downstream regulator bag-1 was also upregulated in OA compared with normal cartilage. Collagen VI was mainly cellassociated in non-OA cartilage, with a more widespread distribution observed in OA cartilage along with increased intracellular staining intensity. The collagen VI integral membrane proteoglycan receptor NG2 was downregulated in advanced OA compared with its patientmatched minimally involved cartilage sample. These results suggest that chondrocytes exhibit ER stress during OA, in association with upregulation of a large secreted molecule, type VI collagen. (J Histochem Cytochem 57:923-931, 2009) K E Y W O R D S osteoarthritis cartilage ER stress bag-1 grp78 collagen VI NG2 OSTEOARTHRITIS (OA) IS A PROGRESSIVE DISEASE, with changes in chondrocyte gene expression and extracellular matrix (ECM) composition occurring before macroscopic structural damage is observed (Hamerman 1989). Articular chondrocytes in OA exhibit a hypermetabolic phenotype, with studies describing highly proliferative clonal chondrocytes, along with the upand downregulation of ECM molecules such as aggrecan

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“…As chondrocyte expression in known to undergo change with the degeneration of articular cartilage, the impact of osteoarthritis in donor cartilage on ACI is also poorly researched in the literature. 15,16 Hence, the objective of this study was to compare the gene expression profiles of OA human cartilage tissue and cultured chondrocytes, and to investigate the effect of increasing passage on the expression of chondrogenic genes in cultured human chondrocytes. The expression patterns of matrix proteins, matrix proteases, protease inhibitors, transcription factors, cytokine/growth factors, and intercellular signaling factors in human articular cartilage and isolated chondrocytes were determined by real-time polymerase chain reaction (PCR).…”

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confidence: 99%

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

Lin

Fitzgerald

et al. 2008

Journal Orthopaedic Research

180

149

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Chondrocyte phenotype has been shown to dedifferentiate during passaged monolayer cultivation. Hence, we have investigated the expression profile of 27 chondrocyte-associated genes from both osteoarthritic cartilage tissue and healthy passaged human articular chondrocytes by quantitative real-time PCR. Our results indicate that the gene expression levels of matrix proteins and proteases in chondrocytes from monolayer culture decrease compared with those from cartilage tissue, while monolayer cultured chondrocytes from normal and osteoarthritic cartilage exhibit similar gene expression patterns. However, chondrocytic gene expression profiles were differentially altered at various stages of passage. The expression of the matrix proteins aggrecan, type II collagen, and fibromodulin inversely correlated with increasing passage number, while fibronectin and link protein exhibited a marked increase with passage. The expression of matrix proteinases MMP-3/9/13 and ADAMTS-4/5 decreased with passage, whereas proteinase inhibitors TIMP-2/3 were elevated. The cytokine IL-1 also showed increased expression with monolayer chondrocyte culture, while IGF-1 expression levels were diminished. No significant changes in TGF-b, or the chondrogenic transcription factors Sox-9, c-fos, or c-jun were observed. Our data indicates that cultured chondrocytes undergo dedifferentiation during monolayer culture, although the gene expression level of transcription factors necessary for chondrogenesis remains unchanged. This data may prove important for the future development of more specific and efficacious cultivation techniques for human articular chondrocyte-based therapies. ß

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Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype

Cited by 84 publications

References 54 publications

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Advanced Osteoarthritis in Humans Is Associated With Altered Collagen VI Expression and Upregulation of ER-stress Markers Grp78 and Bag-1

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

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