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Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1β

Overview of attention for article published in Arthritis Research & Therapy, December 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (63rd percentile)

Mentioned by

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1 news outlet
twitter
1 tweeter

Citations

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16 Dimensions

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33 Mendeley
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Title
Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1β
Published in
Arthritis Research & Therapy, December 2015
DOI 10.1186/s13075-015-0891-z
Pubmed ID
Authors

Clare L. Thompson, Riana Patel, Terri-Ann N. Kelly, Angus K. T. Wann, Clark T. Hung, J. Paul Chapple, Martin M. Knight

Abstract

In osteoarthritis, chondrocytes adopt an abnormal hypertrophic morphology and upregulate the expression of the extracellular matrix-degrading enzymes, MMP-13 and ADAMTS-5. The activation of the hedgehog signalling pathway has been established in osteoarthritis and is thought to influence both of these processes. However, the role of this pathway in the initiation and progression of osteoarthritis is unclear as previous studies have been unable to isolate the effects of hedgehog pathway activation from other pathological processes. In this study we test the hypothesis that hedgehog pathway activation causes cartilage degradation in healthy cartilage and in an in vitro model of inflammatory arthritis. Isolated articular chondrocytes from the bovine metacarpal-phalangeal joint were stimulated for up to 24 hours with the agonist, recombinant Indian hedgehog (r-Ihh). ADAMTS-5 and MMP-13 gene expression was quantified by real-time PCR. In addition, healthy bovine cartilage explants were treated with r-Ihh or the hedgehog antagonist, cyclopamine, and sGAG release into the media was measured over 72 hours. Studies were repeated using chondrocytes and cartilage explants from human knee joint. Finally, studies were conducted to determine the effect of hedgehog pathway activation on matrix catabolism in the presence of the pro-inflammatory cytokine, IL-1β. Addition of r-Ihh activated hedgehog signalling, confirmed by upregulation of Gli1 and Ptch1 expression, but did not increase ADAMTS-5 or MMP-13 expression in bovine or human chondrocytes. Furthermore, r-Ihh did not induce sGAG release in healthy bovine or human cartilage explants. IL-1β treatment induced sGAG release, but this response was not altered by the stimulation or inhibition of hedgehog signalling. Hedgehog pathway activation was downregulated by IL-1β. Conversely, r-Ihh weakly suppressed IL-1β-induced ADAMTS-5 expression. Our results show for the first time that Indian hedgehog does not cause extracellular matrix degradation in healthy ex vivo cartilage or in the presence of IL-1β and that IL-1β downregulates Indian hedgehog induced signalling. Thus, we suggest reported hedgehog induced matrix catabolism in osteoarthritis must be due to its interaction with pathological factors other than IL-1β. Hence, hedgehog signalling and its downstream effects are highly context-dependent.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 6%
Italy 1 3%
Unknown 30 91%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 24%
Student > Bachelor 6 18%
Researcher 5 15%
Student > Ph. D. Student 4 12%
Student > Doctoral Student 3 9%
Other 2 6%
Unknown 5 15%
Readers by discipline Count As %
Engineering 7 21%
Biochemistry, Genetics and Molecular Biology 7 21%
Medicine and Dentistry 4 12%
Agricultural and Biological Sciences 3 9%
Nursing and Health Professions 2 6%
Other 3 9%
Unknown 7 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 December 2015.
All research outputs
#1,432,593
of 12,451,992 outputs
Outputs from Arthritis Research & Therapy
#398
of 1,983 outputs
Outputs of similar age
#49,449
of 344,679 outputs
Outputs of similar age from Arthritis Research & Therapy
#105
of 315 outputs
Altmetric has tracked 12,451,992 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,983 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,679 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 315 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.