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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

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A Correction to this article was published on 19 January 2019

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Abstract

Purpose

To 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.

Methods

Forty-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.

Results

In 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.

Conclusion

GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

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Change history

  • 19 January 2019

    The author ?Ashish D. Diwan? receives educational consultant fees from Nuvasive Inc.

  • 19 January 2019

    The author ���Ashish D. Diwan��� receives educational consultant fees from Nuvasive Inc.

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Acknowledgements

The authors would like to thank Erikka Linn, Edward Abarado, and Weibo Jiang, M.D. for their generous assistance.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA

    Shingo Miyazaki, Kenji Kato, Kevin Cheng, Junichi Yamada, Mary E. Lenz, Robert L. Sah & Koichi Masuda

  2. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho Chuo-Ku, Kobe, 650-0017, Hyogo, Japan

    Shingo Miyazaki

  3. Orthopaedic 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

    Ashish D. Diwan

  4. Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medicine, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Aichi, Japan

    Kenji Kato

  5. Department of Radiology, University of California-San Diego, 9500 Gilman Dr., MC0997, La Jolla, CA, 92093-0997, USA

    Won C. Bae

  6. Department of Bioengineering, University of California-San Diego, 9500 Gilman Dr., MC0412, La Jolla, CA, 92093-0412, USA

    Yang Sun & Robert L. Sah

  7. Orthopaedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, China

    Yang Sun

  8. Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan

    Junichi Yamada

  9. Department of Biochemistry, Rush University Medical Center, 1645 W Harrison St, 5th floor, Chicago, 60612, IL, USA

    Carol Muehleman

  10. Department of Orthopaedic Surgery, Rush University Medical Center, 1611 W. Harrison St. Suite 204J, Chicago, 60612, IL, USA

    Nozomu Inoue

  11. Spine Care Center, Wakayama Medical University Kihoku Hospital, 219, Myouji, Katsuragicho, Ito Gun, 649-7113, Wakayama, Japan

    Mamoru Kawakami

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  1. Shingo Miyazaki
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Correspondence to Koichi Masuda.

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The authors did not receive outside funding or support for this work, and have no actual or potential conflicts of interest to disclose.

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Miyazaki, S., Diwan, A.D., Kato, K. et al. 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. Eur Spine J 27, 739–751 (2018). https://doi.org/10.1007/s00586-018-5488-1

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