Evidence map›Paper›PMID 28705915›Full record

ArticleAnnals of the rheumatic diseases2017

Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation.

Anasuya Kuttapitiya, Lena Assi, Ken Laing, Caroline Hing, Philip Mitchell, Guy Whitley, Abiola Harrison, Franklyn A Howe, Vivian Ejindu, Christine Heron and 1 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05204836 (Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention), which is not on this map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05204836 phase1terminatednot on this mapstarted 2023, after this paper: background citation

Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention

TypeinterventionalSponsorUniversity of CalgaryRan2023 to 2025Enrolled4ConditionsAnterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries, Osteo Arthritis KneeArmsZoledronic Acid Injection, Placebo
3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.

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  14. Osteoarthritis.Nature reviews. Disease primers · 2025
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Anasuya KuttapitiyaInstitute for Infection & Immunity, St George's, University of London, London, UK.
Lena AssiInstitute for Infection & Immunity, St George's, University of London, London, UK.
Ken LaingInstitute for Infection & Immunity, St George's, University of London, London, UK.
Caroline HingSt George's University Hospitals NHS Foundation Trust, London, UK.
Philip MitchellSt George's University Hospitals NHS Foundation Trust, London, UK.
Guy WhitleyInstitute for Molecular and Clinical Sciences, St George's, University of London, London, UK.
Abiola HarrisonInstitute for Infection & Immunity, St George's, University of London, London, UK.
Franklyn A HoweInstitute for Molecular and Clinical Sciences, St George's, University of London, London, UK.
Vivian EjinduSt George's University Hospitals NHS Foundation Trust, London, UK.
Christine HeronSt George's University Hospitals NHS Foundation Trust, London, UK.
Nidhi SofatInstitute for Infection & Immunity, St George's, University of London, London, UK.
St George's, University of London · GBSt George’s University Hospitals NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveBone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression.

methodsWe recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray.

resultsThe mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p<0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways.

conclusionOur study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.

Indexed as

AdultAgedAged, 80 and overArthroplasty, Replacement, KneeBone MarrowBone RemodelingChondrogenesisFemaleGene Expression ProfilingHumansInflammationMagnetic Resonance ImagingMaleMiddle AgedNeurogenesisOsteoarthritis, KneeChemokinesChondrocytesInflammationKnee OsteoarthritisMagnetic Resonance Imaging

Identifiers

PMID28705915
PMCPMC5629942
OpenAlexW2625972055

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.