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Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration

Overview of attention for article published in Arthritis Research & Therapy, May 2015
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Title
Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration
Published in
Arthritis Research & Therapy, May 2015
DOI 10.1186/s13075-015-0625-2
Pubmed ID
Authors

Nicole Willems, Frances C Bach, Saskia G M Plomp, Mattie HP van Rijen, Jeannette Wolfswinkel, Guy CM Grinwis, Clemens Bos, Gustav J Strijkers, Wouter JA Dhert, Björn P Meij, Laura B Creemers, Marianna A Tryfonidou

Abstract

Strategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain. Canine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue. In vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7. An intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 58 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 16%
Researcher 8 14%
Other 6 10%
Student > Bachelor 5 9%
Student > Ph. D. Student 5 9%
Other 13 22%
Unknown 12 21%
Readers by discipline Count As %
Medicine and Dentistry 19 33%
Veterinary Science and Veterinary Medicine 8 14%
Agricultural and Biological Sciences 7 12%
Engineering 6 10%
Nursing and Health Professions 3 5%
Other 2 3%
Unknown 13 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 June 2015.
All research outputs
#17,285,668
of 25,374,647 outputs
Outputs from Arthritis Research & Therapy
#2,536
of 3,381 outputs
Outputs of similar age
#167,878
of 280,163 outputs
Outputs of similar age from Arthritis Research & Therapy
#43
of 62 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% 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 16th percentile – i.e., 16% 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 280,163 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 62 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.