Blood-based biomarkers for detecting mild osteoarthritis in the human knee

Marshall, K. W.; Zhang, H.; Yager, Tom; Nossova, Nadine; Dempsey, Adam A.; Zheng, Run; Han, Mark; Tang, Hong-Chang; Chao, Samuel T.; Liew, Choong Chin

doi:10.1016/j.joca.2005.06.002

Cited by 44 publications

(27 citation statements)

References 41 publications

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“…Both proteins showed a considerable fold change in our analysis (1.8 and 3, respectively), and had a considerable number of interacting partners in the network analysis (six and seven, respectively) suggesting that expression changes are likely to have a substantial impact on cellular processes including apoptosis. Also MAFB and EGR1 , identified previously as biomarkers in blood expression profiles of patients with mild knee osteoarthritis,34 were differentially expressed in our dataset. Taken together, the overlap between our analysis and other studies confirms that osteoarthritis-specific gene expression profiles of PBMC exist.…”

Section: Discussionmentioning

confidence: 70%

Genes expressed in blood link osteoarthritis with apoptotic pathways

Ramos

Bos

Lakenberg

et al. 2014

Annals of the Rheumatic Diseases

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In the current study, we have identified specific gene expression networks, in the easily accessible tissue blood, which associated consistently with osteoarthritis among GARP study cases. Our data further hint at the relevance of apoptosis as an aetiological factor in osteoarthritis onset, thereby qualifying expression profiling of blood as a useful tool to understand the underlying molecular mechanisms of osteoarthritis.

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Section: Discussionmentioning

confidence: 70%

Genes expressed in blood link osteoarthritis with apoptotic pathways

Ramos

Bos

Lakenberg

et al. 2014

Annals of the Rheumatic Diseases

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“…Unsupervised clustering demonstrated that while contralateral samples were different from shamoperated samples, heterogeneity among contralateral samples was present, with some animals showing greater dysregulation than others. Differences in gene expression in the contralateral and sham-operated samples could be due to altered biomechanics (e.g., altered loading of the contralateral joint) or to systemic factors (e.g., mediators of inflammation) released as OA progresses in the ipsilateral joint (57). Further, differences in compensatory contralateral joint loading between individuals may account for heterogeneity among contralateral samples.…”

Section: Discussionmentioning

confidence: 99%

Global analyses of gene expression in early experimental osteoarthritis

Appleton¹,

Pitelka²,

Henry³

et al. 2007

Arthritis & Rheumatism

223

224

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Objective. To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis.Methods. OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.Results. After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >1.5-fold, 722 with changes >2-fold, 135 with changes >4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control.Conclusion. Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.

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“…Using a genomic approach based on isolation of mRNA from circulating blood and subsequent reverse transcription polymerase chain reaction, Marshall et al [2] identified six genes which were significantly downregulated in patients with mild osteoarthritis (according to arthroscopy assessment) compared with healthy controls. Combination of these six genes in a multiple variable model was able to correctly identify 85% with mild osteoarthritis and controls.…”

Section: New Methodologies and New Biochemical Markersmentioning

confidence: 99%

Use of biochemical markers to study and follow patients with osteoarthritis

Garnero¹

2006

Curr Rheumatol Rep

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Osteoarthritis is characterized by progressive destruction of articular cartilage and subchondral bone and synovial reaction. Radiologic findings that form the basis of the diagnosis of osteoarthritis are poorly sensitive to detect early disease and for monitoring progression of joint damage. Blood-based proteomic analyses suggest that biochemical alterations can be observed well before radiologic damage is evidenced. New cartilage-specific markers, including assays for type II collagen synthesis and degradation, have been developed. Recent prospective studies indicate that blood and urine levels of these new markers are associated with progression of joint damage. Biological markers respond rapidly to treatment and therefore will certainly play an important role in the development and the monitoring of disease-modifying therapies. Because osteoarthritis involves different tissues and complex biologic processes, a combination of different biochemical markers appears to be the most promising diagnostic strategy.

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Blood-based biomarkers for detecting mild osteoarthritis in the human knee

Abstract: Linear combinations of blood RNA biomarkers offer a substantial improvement over currently available diagnostic tools for mild OA. Blood-derived RNA biomarkers may be of significant clinical value for the diagnosis of early, asymptomatic OA of the knee.

Cited by 44 publications

References 41 publications

Genes expressed in blood link osteoarthritis with apoptotic pathways

Genes expressed in blood link osteoarthritis with apoptotic pathways

Global analyses of gene expression in early experimental osteoarthritis

Use of biochemical markers to study and follow patients with osteoarthritis

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