Evidence map›Paper›PMID 29891135›Full record

ArticleJournal of autoimmunity2018

11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.

R S Hardy, C Fenton, A P Croft, A J Naylor, R Begum, G Desanti, C D Buckley, G Lavery, M S Cooper, K Raza

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of autoimmunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 35 citations in OpenAlex.

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  4. Context-dependent roles of 11β-HSD1 in bone and skeletal muscle diseases.American journal of translational research · 2026
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  12. Effects ofFrontiers in bioengineering and biotechnology · 2022
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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

10 authors at 5 institutions in 2 countries.

R S HardyInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. Electronic address: r.hardy@bham.ac.uk.
C FentonInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
A P CroftInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK.
A J NaylorInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK.
R BegumInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
G DesantiInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK.
C D BuckleyInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK.
G LaveryInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, UK.
M S CooperANZAC Research Institute, University of Sydney, Sydney, Australia.
K RazaInstitute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, MRC ARUK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, UK; Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
University of Birmingham · GBArthritis UK · GBOxford Centre for Diabetes, Endocrinology and Metabolism · GBSandwell & West Birmingham Hospitals NHS Trust · GBThe University of Sydney · AU

Funding

Arthritis Research UK 19859Arthritis Research UK 20843Biotechnology and Biological Sciences Research Council BB/G023468/1Medical Research Council MR/P021220/1Versus Arthritis 19859Versus Arthritis 20843Versus Arthritis 21743
6 · The paper itself

Abstract

objectiveIn rheumatoid arthritis, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is highly expressed at sites of inflammation, where it converts inactive glucocorticoids (GC) to their active counterparts. In conditions of GC excess it has been shown to be a critical regulator of muscle wasting and bone loss. Here we examine the contribution of 11β-HSD1 to the pathology of persistent chronic inflammatory disease.

methodsTo determine the contribution of 11β-HSD1 to joint inflammation, destruction and systemic bone loss associated with persistent inflammatory arthritis, we generated mice with global and mesenchymal specific 11β-HSD1 deletions in the TNF-transgenic (TNF-tg) model of chronic polyarthritis. Disease severity was determined by clinical scoring. Histology was assessed in formalin fixed sections and fluorescence-activated cell sorting (FACS) analysis of synovial tissue was performed. Local and systemic bone loss were measured by micro computed tomography (micro-CT). Measures of inflammation and bone metabolism were assessed in serum and in tibia mRNA.

resultsGlobal deletion of 11β-HSD1 drove an enhanced inflammatory phenotype, characterised by florid synovitis, joint destruction and systemic bone loss. This was associated with increased pannus invasion into subchondral bone, a marked polarisation towards pro-inflammatory M1 macrophages at sites of inflammation and increased osteoclast numbers. Targeted mesenchymal deletion of 11β-HSD1 failed to recapitulate this phenotype suggesting that 11β-HSD1 within leukocytes mediate its protective actions in vivo.

conclusionsWe demonstrate a fundamental role for 11β-HSD1 in the suppression of synovitis, joint destruction, and systemic bone loss. Whilst a role for 11β-HSD1 inhibitors has been proposed for metabolic complications in inflammatory diseases, our study suggests that this approach would greatly exacerbate disease severity.

Indexed as

11-beta-Hydroxysteroid Dehydrogenase Type 1AnimalsArthritisArthritis, RheumatoidBone ResorptionChronic DiseaseDisease Models, AnimalGlucocorticoidsHumansInflammationJointsMacrophagesMiceMice, Inbred C57BLMice, TransgenicOsteoclasts11-beta-Hydroxysteroid Dehydrogenase Type 1GlucocorticoidsTNF protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID29891135
PMCPMC6066611
OpenAlexW2807618713

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.