Extending the Paradigm of Osteoarthritis: Comment on the Editorial by McAlindon

Hardingham, Timothy E.

doi:10.1002/art.39500

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…30 46 Many failed clinical trials in knee OA have possibly benefited some patients, but had poor success overall and have not delivered clear benefit above placebo within the time frame of the trial. [47][48][49] The results in this study identify a metabolic basis for stratifying patients into two groups, which are based on major differences in gene expression. While these changes are specific to chondrocytes in cartilage they may also reflect responses to mechanical signals and biological mediators from across the joint.…”

Section: Discussionmentioning

confidence: 87%

Faculty Opinions recommendation of Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage.

Vincent

2019

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Introduction osteoarthritis (oA) is a heterogeneous and complex disease. We have used a network biology approach based on genome-wide analysis of gene expression in oA knee cartilage to seek evidence for pathogenic mechanisms that may distinguish different patient subgroups. Methods results from rnA-Sequencing (rnA-Seq) were collected from intact knee cartilage at total knee replacement from 44 patients with oA, from 16 additional patients with oA and 10 control patients with non-oA. results were analysed to identify patient subsets and compare major active pathways. results the rnA-Seq results showed 2692 differentially expressed genes between oA and non-oA. Analysis by unsupervised clustering identified two distinct oA groups: Group A with 24 patients (55%) and Group B with 18 patients (41%). A 10 gene subgroup classifier was validated by rt-qpCr in 16 further patients with oA. pathway analysis showed increased protein expression in both groups. phenomeExpress analysis revealed group differences in complement activation, innate immune responses and altered Wnt and tGFβ signalling, but no activation of inflammatory cytokine expression. Both groups showed suppressed circadian regulators and whereas matrix changes in Group A were chondrogenic, in Group B they were non-chondrogenic with changes in mechanoreceptors, calcium signalling, ion channels and in cytoskeletal organisers. the gene expression changes predicted 478 potential biomarkers for detection in synovial fluid to distinguish patients from the two groups. conclusions two subgroups of knee oA were identified by network analysis of rnA-Seq data with evidence for the presence of two major pathogenic pathways. this has potential importance as a new basis for the stratification of patients with oA for drug trials and for the development of new targeted treatments.

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Section: Discussionmentioning

confidence: 87%

Faculty Opinions recommendation of Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage.

Vincent

2019

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage

et al. 2017

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IntroductionOsteoarthritis (OA) is a heterogeneous and complex disease. We have used a network biology approach based on genome-wide analysis of gene expression in OA knee cartilage to seek evidence for pathogenic mechanisms that may distinguish different patient subgroups.MethodsResults from RNA-Sequencing (RNA-Seq) were collected from intact knee cartilage at total knee replacement from 44 patients with OA, from 16 additional patients with OA and 10 control patients with non-OA. Results were analysed to identify patient subsets and compare major active pathways.ResultsThe RNA-Seq results showed 2692 differentially expressed genes between OA and non-OA. Analysis by unsupervised clustering identified two distinct OA groups: Group A with 24 patients (55%) and Group B with 18 patients (41%). A 10 gene subgroup classifier was validated by RT-qPCR in 16 further patients with OA. Pathway analysis showed increased protein expression in both groups. PhenomeExpress analysis revealed group differences in complement activation, innate immune responses and altered Wnt and TGFβ signalling, but no activation of inflammatory cytokine expression. Both groups showed suppressed circadian regulators and whereas matrix changes in Group A were chondrogenic, in Group B they were non-chondrogenic with changes in mechanoreceptors, calcium signalling, ion channels and in cytoskeletal organisers. The gene expression changes predicted 478 potential biomarkers for detection in synovial fluid to distinguish patients from the two groups.ConclusionsTwo subgroups of knee OA were identified by network analysis of RNA-Seq data with evidence for the presence of two major pathogenic pathways. This has potential importance as a new basis for the stratification of patients with OA for drug trials and for the development of new targeted treatments.

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Extending the Paradigm of Osteoarthritis: Comment on the Editorial by McAlindon

Cited by 2 publications

References 19 publications

Faculty Opinions recommendation of Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage.

Faculty Opinions recommendation of Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage.

Stratification of knee osteoarthritis: two major patient subgroups identified by genome-wide expression analysis of articular cartilage

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