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Evaluation of Salivary Cytokines for Diagnosis of both Trauma-Induced and Genetic Heterotopic Ossification

Overview of attention for article published in Frontiers in endocrinology, April 2017
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  • Good Attention Score compared to outputs of the same age (68th percentile)
  • Good Attention Score compared to outputs of the same age and source (69th percentile)

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Title
Evaluation of Salivary Cytokines for Diagnosis of both Trauma-Induced and Genetic Heterotopic Ossification
Published in
Frontiers in endocrinology, April 2017
DOI 10.3389/fendo.2017.00074
Pubmed ID
Authors

Hsiao Hsin Sung Hsieh, Michael T. Chung, Ronald M. Allen, Kavitha Ranganathan, Joe Habbouche, David Cholok, Jonathan Butts, Arminder Kaura, Ramkumar Tiruvannamalai-Annamalai, Chris Breuler, Caitlin Priest, Shawn J. Loder, John Li, Shuli Li, Jan Stegemann, Steven L. Kunkel, Benjamin Levi

Abstract

Heterotopic ossification (HO) occurs in the setting of persistent systemic inflammation. The identification of reliable biomarkers can serve as an early diagnostic tool for HO, especially given the current lack of effective treatment strategies. Although serum biomarkers have great utility, they can be inappropriate or ineffective in traumatic acute injuries and in patients with fibrodysplasia ossificans progressiva (FOP). Therefore, the goal of this study is to profile the cytokines associated with HO using a different non-invasive source of biomarkers. Serum and saliva were collected from a model of trauma-induced HO (tHO) with hind limb Achilles' tenotomy and dorsal burn injury at indicated time points (pre-injury, 48 h, 1 week, and 3 weeks post-injury) and a genetic non-trauma HO model (Nfatc1-Cre/caAcvr1(fl/wt) ). Samples were analyzed for 27 cytokines using the Bio-Plex assay. Histologic evaluation was performed in Nfatc1-Cre/caAcvr1(fl/wt) mice and at 48 h and 1 week post-injury in burn tenotomy mice. The mRNA expression levels of these cytokines at the tenotomy site were also quantified with quantitative real-time PCR. Pearson correlation coefficient was assessed between saliva and serum. Levels of TNF-α and IL-1β peaked at 48 h and 1 week post-injury in the burn/tenotomy cohort, and these values were significantly higher when compared with both uninjured (p < 0.01, p < 0.03) and burn-only mice (p < 0.01, p < 0.01). Immunofluorescence staining confirmed enhanced expression of IL-1β, TNF-α, and MCP-1 at the tenotomy site 48 h after injury. Monocyte chemoattractant protein-1 (MCP-1) and VEGF was detected in saliva showing elevated levels at 1 week post-injury in our tHO model when compared with both uninjured (p < 0.001, p < 0.01) and burn-only mice (p < 0.005, p < 0.01). The Pearson correlation between serum MCP-1 and salivary MCP-1 was statistically significant (r = 0.9686, p < 0.001) Similarly, the Pearson correlation between serum VEGF and salivary VEGF was statistically significant (r = 0.9709, p < 0.05). In this preliminary study, we characterized the diagnostic potential of specific salivary cytokines that may serve as biomarkers for an early-stage diagnosis of HO. This study identified two candidate biomarkers for further study and suggests a novel method for diagnosis in the context of current difficult diagnosis and risks of current diagnostic methods in certain patients.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 40 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 15%
Other 5 13%
Student > Bachelor 4 10%
Student > Doctoral Student 4 10%
Professor 3 8%
Other 5 13%
Unknown 13 33%
Readers by discipline Count As %
Medicine and Dentistry 10 25%
Engineering 6 15%
Biochemistry, Genetics and Molecular Biology 5 13%
Chemical Engineering 1 3%
Immunology and Microbiology 1 3%
Other 3 8%
Unknown 14 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 13 June 2023.
All research outputs
#6,755,994
of 25,382,440 outputs
Outputs from Frontiers in endocrinology
#1,803
of 13,018 outputs
Outputs of similar age
#99,421
of 323,377 outputs
Outputs of similar age from Frontiers in endocrinology
#23
of 76 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 13,018 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done well, scoring higher than 86% 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 323,377 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 76 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 69% of its contemporaries.