Evidence map›Paper›PMID 29460012›Full record

ArticleEuropean spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society2018

ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

Shingo Miyazaki, Ashish D Diwan, Kenji Kato, Kevin Cheng, Won C Bae, Yang Sun, Junichi Yamada, Carol Muehleman, Mary E Lenz, Nozomu Inoue and 3 more

Erratum issued Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07668466 (A Phase I/II, Open-label, Single Administration Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of Intradiscal rhGDF-6 for the Treatment of Lumbar Disc Degeneration), which is not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.0field-weighted citation impact, top 9% 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.

NCT07668466 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase I/II, Open-label, Single Administration Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of Intradiscal rhGDF-6 for the Treatment of Lumbar Disc Degeneration

TypeinterventionalSponsorCartago Biotech Pty LtdRan2026 to 2030Enrolled60ConditionsDisc Degenerative Disease, Back PainArmsHigh Dose, Low Dose
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Review
  3. Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
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  7. Article
  8. Review
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  12. Review
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  15. Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus.International journal of molecular sciences · 2020
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 4 countries.

Shingo MiyazakiDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Ashish D DiwanOrthopaedic Research Institute and Department of Orthopaedic Surgery, St George Hospital, University of New South Wales, Suite 16, Lvl 5, 1 South Street, Kogarah, Sydney, NSW 2217, Australia.
Kenji KatoDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Kevin ChengDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Won C BaeDepartment of Radiology, University of California-San Diego, 9500 Gilman Dr., MC0997, La Jolla, CA, 92093-0997, USA.
Yang SunDepartment of Bioengineering, University of California-San Diego, 9500 Gilman Dr., MC0412, La Jolla, CA, 92093-0412, USA.
Junichi YamadaDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Carol MuehlemanDepartment of Biochemistry, Rush University Medical Center, 1645 W Harrison St, 5th floor, Chicago, 60612, IL, USA.
Mary E LenzDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Nozomu InoueDepartment of Orthopaedic Surgery, Rush University Medical Center, 1611 W. Harrison St. Suite 204J, Chicago, 60612, IL, USA.
Robert L SahDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.
Mamoru KawakamiSpine Care Center, Wakayama Medical University Kihoku Hospital, 219, Myouji, Katsuragicho, Ito Gun, 649-7113, Wakayama, Japan.
Koichi MasudaDepartment of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA. komasuda@ucsd.edu.ORCID http://orcid.org/0000-0002-5361-4415
University of California San Diego · USRush University Medical Center · USMie University · JPNagoya City University · JPUNSW Sydney · AUWakayama Medical University · JP

Funding

Diversity Supplement -"Bioinspired Synthetic Grafts for Bone Regeneration"R01AR063184 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARGHESE, SHYNI · 2013 to 2017
$1.7M
NIAMS NIH HHS R01 AR063184
6 · The paper itself

Abstract

purposeTo elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model.

methodsForty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically.

resultsIn GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group.

conclusionGDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Indexed as

AnimalsAwards and PrizesCalcitonin Gene-Related PeptideCalcium-Binding ProteinsCytokinesDisease Models, AnimalFemaleGanglia, SpinalGrowth Differentiation Factor 6HeterograftsHyperalgesiaImmunohistochemistryIntervertebral DiscIntervertebral Disc DegenerationMagnetic Resonance ImagingMicrofilament ProteinsAif1 protein, ratCalcitonin Gene-Related PeptideCalcium-Binding ProteinsCytokinesGrowth Differentiation Factor 6Microfilament ProteinsNerve Growth FactorProstaglandin-Endoperoxide SynthasesVascular Endothelial Growth Factor AGrowth differentiation factor-6Inflammatory cytokinesIntervertebral disc degenerationPain behaviorRabbit anular-puncture modelRat xenograft radiculopathy model

Identifiers

PMID29460012
PMCPMC5874179
OpenAlexW2792474122

What OpenQuestion holds

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Registered trials

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.