Chondrocyte gene expression in osteoarthritis: Correlation with disease severity

Eid, Karim; Thornhill, Thomas S.; Glowacki, Julie

doi:10.1002/jor.20137

Cited by 29 publications

(29 citation statements)

References 18 publications

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“…This may reflect differences in dog age and/or breeds or variation in the time from surgical removal to collection in the preservative fluid. The analysis of additional samples or the phenotyping and selection of samples through histological grading may have increased the statistical powers of each of these differences observed, as the severity of OA measured by histology (Mankin score) correlates with a reduction in the expression of COL2 and AGC [27]. …”

Section: Discussionmentioning

confidence: 99%

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et al. 2006

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The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised that the expression of selected proteases, matrix molecules, and collagens believed to have a role in the pathogenesis of OA would be changed in naturally occurring canine OA cartilage when compared to normal articular cartilage. Quantitative (real-time) reverse transcriptasepolymerase chain reaction assays were designed measuring the expression of selected matrix molecules (collagens and small leucine-rich proteoglycans), key mediators of the proteolytic degradation of articular cartilage (metalloproteinases, cathepsins), and their inhibitors (tissue inhibitors of matrix metalloproteinases). All data were normalised using a geometric mean of three housekeeping genes, and the results subjected to power calculations and corrections for multiple hypothesis testing. We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1, CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA. The expression of TIMP2 and TIMP4 was significantly reduced in canine OA cartilage. The patterns of gene expression change observed in naturally occurring canine OA were similar to those reported in naturally occurring human OA and experimental canine OA. We conclude that the expression profiles of matrix-associated molecules in end-stage mammalian OA may be comparable but that the precise aetiologies of OA affecting specific joints in different species are presently unknown.

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Section: Discussionmentioning

confidence: 99%

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et al. 2006

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“…In addition to the degradation by cartilage aggrecanases which play a critical role in the development of OA (Malfait et al, 2002, Song et al, 2007), decreased aggrecan expression is often evident in OA cartilage (Chambers et al, 2002, Eid et al, 2006). The expression of SIRT1, a member of HDACs, is decreased in human OA cartilage, and inhibition of SIRT1 significantly decreases the expression of aggrecan in both normal and OA human chondrocytes (Fujita et al, 2011).…”

Section: Epigenetic Mechanisms Underlying the Aberrant Metabolic Amentioning

confidence: 99%

Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes

Zhang¹,

Egan²,

Wang

2015

The International Journal of Biochemistry & Cell Biology

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The development of disease-modifying pharmacologic therapy for osteoarthritis currently faces major obstacles largely because the pathogenetic mechanisms for development of osteoarthritis remain unclear. Previous studies suggest that the alterations in expression of catabolic and anabolic genes in articular chondrocytes may be involved in the pathogenesis of osteoarthritis. However, the regulatory mechanisms for gene expression in osteoarthritic chondrocytes are largely unknown. The objective of this review is to highlight the recent studies on epigenetic regulation of gene expression in the development of osteoarthritis. The review will begin with current understanding of epigenetic mechanisms, especially the newly emerging areas including the regulatory role of non-coding RNAs in gene expression and crosstalk among the epigenetic mechanisms. The main content of this review focuses on the significance of epigenetic regulation of the expression of catabolic and anabolic genes in osteoarthritic chondrocytes, including the regulatory roles of various epigenetic mechanisms in the expression of genes for specific matrix-degrading proteinases, cytokines, and extracellular matrix proteins. Recent novel findings on the epigenetic regulation of specific transcription factor genes are particularly important for the understanding of osteoarthritis pathogenesis, as these transcription factors may act as upstream regulators of multiple catabolic and anabolic genes. In conclusion, these recent advances in epigenetic studies have shed light on the importance of epigenetic regulation of gene expression in the development of osteoarthritis, leading to a better understanding of the epigenetic mechanisms underlying the pathogenesis of osteoarthritis. This may promote the development of new epigenetics-based strategies for the treatment of osteoarthritis.

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“…10 The samples with Mankin score 10-14 were collected as the advanced OA cartilage (AOC) group. 7,8,11 Normal articular cartilage (NAC) was obtained from the femoral condyle of 22 patients [3 males, 19 females; average age: 50.5 years old (42-68 years old)]. Six were taken from the operation of amputation because of femoral artery embolism and the other 16 from the donors within 8 h after death.…”

Section: Cartilage Samplesmentioning

confidence: 99%

“…7,8 Chondrocyte phenotype alternations serve as an important cellular event in OA progression, however,…”

mentioning

confidence: 99%

“…2 However, as OA progresses to an advanced stage, chondrocytes begin to express heterogenous phenotypes representatively, type X collagen, 3−6 in conjunction with decreases in type II collagen and aggrecan expression, which reduces the capability of the OA cartilage to repair lesions naturally. 7,8 Chondrocyte phenotype alternations serve as an important cellular event in OA progression, however, little is known about the underlying mechanisms. This study aims to understand molecules that involved in phenotype regulation of OA chondrocytes.…”

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confidence: 99%

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REST corepressor (CoREST) repression induces phenotypic gene regulation in advanced osteoarthritic chondrocytes

Xiao

et al. 2010

Journal Orthopaedic Research

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Alternations in cartilage chondrocyte phenotype characteristic by the decreased type II collagen and aggrecan together with increased type X collagen synthesis serve as a beacon for osteoarthritis progression. However, little is known about the underlying molecular mechanisms. The current study seeks to discover molecules that involved in osteoarthritic chondrocytes phenotype regulation. Differential proteomics was generated with two-dimensional gel electrophoresis between normal articular cartilage (NAC) and advanced osteoarthritic cartilage (AOC). Those differentially expressed proteins were identified by mass spectrometry. The down-regulation of a neuronal silencer, the REST corepressor (CoREST) in AOC, was verified by Western blot. CoREST silencing was performed in primarily cultured NAC chondrocytes with specific siRNA to reveal the possible involvement of CoREST repression in chondrocyte phenotypic genes modulation. Ninteen differentially expressed proteins were screened and identified. Among these proteins, CoREST, HHL, and zinc finger protein 155 were estimated to be possible gene modulators. CoREST protein level was verified to be down-regulated by 69.5% (p < 0.001) in AOC. In response to CoREST knock-down by 64.8% (p < 0.001) in NAC chondrocytes, the gene expression level of the chondrocyte terminal differentiation marker gene, collagen X was found to be up-regulated by 40.0% (p = 0.017), whereas the chondrocyte differentiation phenotypic genes, collagen II and aggrecan were down-regulated by 71.4% (p < 0.001) and 57.6% (p < 0.001), respectively. The results indicate that the silencing of CoREST by siRNA transfection in NAC may reflect CoREST repression in AOC, which results in phenotypic genes modulation and suggests a homeostatic role of this transcription factor in articular chondrocyte. © Osteoarthritis (OA) is a disease characteristic of progressive cartilage degeneration and abrasion. The central pathogenesis underlying cartilage degeneration is the imbalance between cartilage matrix proteins synthesis and catabolism, 1 whereby the pathobiology of osteoarthritic chondrocytes is of a central concern. Aside from the increased degradative enzyme activity, the phenotype alternations of chondrocytes in advanced OA cartilage lead to hypoactive anabolism, which serves as an important mechanism for OA progression. 1The normal articular chondrocytes are characteristic of phenotypic type II collagen and aggrecan expression. In the early process of OA, articular chondrocytes increase type II collagen and aggrecan synthesis in an attempt to repair cartilage lesions.2 However, as OA progresses to an advanced stage, chondrocytes begin to express heterogenous phenotypes representatively, type X collagen, 3−6 in conjunction with decreases in type II collagen and aggrecan expression, which reduces the capability of the OA cartilage to repair lesions naturally. 7,8 Chondrocyte phenotype alternations serve as an important cellular event in OA progression, however,

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Chondrocyte gene expression in osteoarthritis: Correlation with disease severity

Cited by 29 publications

References 18 publications

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Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes

REST corepressor (CoREST) repression induces phenotypic gene regulation in advanced osteoarthritic chondrocytes

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