Evidence map›Paper›PMID 26013758›Full record

ArticleArthritis research & therapy2015

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

Nicole Willems, Frances C Bach, Saskia G M Plomp, Mattie H P van Rijen, Jeannette Wolfswinkel, Guy C M Grinwis, Clemens Bos, Gustav J Strijkers, Wouter J A Dhert, Björn P Meij and 2 more

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Injectable Biologics for the Treatment of Degenerative Disc Disease.Current reviews in musculoskeletal medicine · 2020
    Review
  15. Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration.International journal of molecular sciences · 2020
    Article
  16. Article
  17. Article
  18. Intervertebral Disc Nucleus Repair: Hype or Hope?International journal of molecular sciences · 2019
    Review
  19. The future of disc surgery and regeneration.International orthopaedics · 2019
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Nicole WillemsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. N.Willems@uu.nl.
Frances C BachDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. F.C.Bach@uu.nl.
Saskia G M PlompDepartment of Orthopaedics, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. S.G.M.Plomp@uu.nl.
Mattie H P van RijenDepartment of Orthopaedics, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. M.Rijen@umcutrecht.nl.
Jeannette WolfswinkelDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. J.Wolfswinkel@uu.nl.
Guy C M GrinwisDepartment of Pathobiology, Faculty of Veterinary Medicine, Yalelaan 1, 3584 CL, Utrecht, The Netherlands. G.C.M.Grinwis@uu.nl.
Clemens BosDepartment of Radiotherapy, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. C.Bos@umcutrecht.nl.
Gustav J StrijkersDepartment of Biomedical Engineering, University of Technology (TU/e), P.O. Box 513, 5600 MB, Eindhoven, The Netherlands. G.J.Strijkers@tue.nl.
Wouter J A DhertDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. W.J.A.Dhert@uu.nl.
Björn P MeijDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. B.P.Meij@uu.nl.
Laura B CreemersDepartment of Orthopaedics, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. L.B.Creemers@umcutrecht.nl.
Marianna A TryfonidouDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Yalelaan 108, 3584 CM, Utrecht, The Netherlands. M.A.Tryfonidou@uu.nl.
Utrecht University · NLHeidelberg University · DEEindhoven University of Technology · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionStrategies 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.

methodsCanine 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.

resultsIn 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.

conclusionsAn 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.

Indexed as

AnimalsBone Morphogenetic Protein 7Disease Models, AnimalDogsIntervertebral Disc DegenerationMaleOsteogenesisPolymerase Chain ReactionBMP7 protein, humanBone Morphogenetic Protein 7

Identifiers

PMID26013758
PMCPMC4443547
OpenAlexW1539484762

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.