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IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis

Overview of attention for article published in Arthritis Research & Therapy, May 2016
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Title
IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis
Published in
Arthritis Research & Therapy, May 2016
DOI 10.1186/s13075-016-0998-x
Pubmed ID
Authors

Anita T. Shaw, Yukiko Maeda, Ellen M. Gravallese

Abstract

Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formation in an in vivo model of inflammatory arthritis. K/BxN serum transfer arthritis was induced in IL-17A-deficient and wild-type mice. Clinical and histologic inflammation was assessed and periosteal bone formation was quantitated. Murine calvarial osteoblasts were differentiated in the continuous presence of IL-17A with or without blockade of secreted frizzled related protein (sFRP)1 and effects on differentiation were determined by qRT-PCR and mineralization assays. The impact of IL-17A on expression of Wnt signaling pathway antagonists was also assessed by qRT-PCR. Finally, regulation of Dickkopf (DKK)1 expression in murine synovial fibroblasts was evaluated after treatment with IL-17A, TNF, or IL-17A plus TNF. IL-17A-deficient mice develop significantly more periosteal bone than wild-type mice at peak inflammation, despite comparable severity of inflammation and bone erosion. IL-17A inhibits calvarial osteoblast differentiation in vitro, inducing mRNA expression of the Wnt antagonist sFRP1 in osteoblasts, and suppressing sFRP3 expression, both potentially contributing to inhibition of osteoblast differentiation. Furthermore, a blocking antibody to sFRP1 reduced the inhibitory effect of IL-17A on differentiation. Although treatment with IL-17A suppresses DKK1 mRNA expression in osteoblasts, IL-17A plus TNF synergistically upregulate DKK1 mRNA expression in synovial fibroblasts. IL-17A may limit the extent of bone formation at inflamed periosteal sites in spondyloarthritis. IL-17A inhibits calvarial osteoblast differentiation, in part by regulating expression of Wnt signaling pathway components. These results demonstrate that additional studies focusing on the role of IL-17A in bone formation in spondyloarthritis are indicated.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 51 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 22%
Student > Ph. D. Student 7 14%
Student > Bachelor 6 12%
Student > Master 6 12%
Student > Doctoral Student 3 6%
Other 4 8%
Unknown 14 27%
Readers by discipline Count As %
Medicine and Dentistry 15 29%
Biochemistry, Genetics and Molecular Biology 10 20%
Agricultural and Biological Sciences 5 10%
Immunology and Microbiology 2 4%
Neuroscience 2 4%
Other 3 6%
Unknown 14 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 May 2016.
All research outputs
#14,599,900
of 25,373,627 outputs
Outputs from Arthritis Research & Therapy
#2,123
of 3,381 outputs
Outputs of similar age
#153,771
of 319,076 outputs
Outputs of similar age from Arthritis Research & Therapy
#28
of 54 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 36th percentile – i.e., 36% 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 319,076 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 50% of its contemporaries.
We're also able to compare this research output to 54 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.