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Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Overview of attention for article published in RMD Open, July 2017
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Title
Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis
Published in
RMD Open, July 2017
DOI 10.1136/rmdopen-2017-000456
Pubmed ID
Authors

Moeed Akbar, Derek S Gilchrist, Susan M Kitson, Briana Nelis, Lindsay A N Crowe, Emma Garcia-Melchor, James H Reilly, Shauna C Kerr, George A C Murrell, Iain B McInnes, Neal L Millar

Abstract

To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 69 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 16%
Student > Ph. D. Student 10 14%
Student > Bachelor 8 12%
Student > Master 6 9%
Student > Doctoral Student 4 6%
Other 10 14%
Unknown 20 29%
Readers by discipline Count As %
Medicine and Dentistry 22 32%
Biochemistry, Genetics and Molecular Biology 9 13%
Nursing and Health Professions 4 6%
Immunology and Microbiology 4 6%
Agricultural and Biological Sciences 3 4%
Other 5 7%
Unknown 22 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 03 August 2017.
All research outputs
#15,237,882
of 25,476,463 outputs
Outputs from RMD Open
#803
of 1,109 outputs
Outputs of similar age
#170,577
of 326,987 outputs
Outputs of similar age from RMD Open
#11
of 22 outputs
Altmetric has tracked 25,476,463 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,109 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.6. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
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 326,987 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 22 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 50% of its contemporaries.