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.

Autor: Miyazaki S; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.; Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho Chuo-Ku, Kobe, 650-0017, Hyogo, Japan., Diwan AD; 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., Kato K; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.; Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medicine, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Aichi, Japan., Cheng K; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA., Bae WC; Department of Radiology, University of California-San Diego, 9500 Gilman Dr., MC0997, La Jolla, CA, 92093-0997, USA., Sun Y; Department of Bioengineering, University of California-San Diego, 9500 Gilman Dr., MC0412, La Jolla, CA, 92093-0412, USA.; Orthopaedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, China., Yamada J; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.; Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan., Muehleman C; Department of Biochemistry, Rush University Medical Center, 1645 W Harrison St, 5th floor, Chicago, 60612, IL, USA., Lenz ME; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA., Inoue N; Department of Orthopaedic Surgery, Rush University Medical Center, 1611 W. Harrison St. Suite 204J, Chicago, 60612, IL, USA., Sah RL; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA.; Department of Bioengineering, University of California-San Diego, 9500 Gilman Dr., MC0412, La Jolla, CA, 92093-0412, USA., Kawakami M; Spine Care Center, Wakayama Medical University Kihoku Hospital, 219, Myouji, Katsuragicho, Ito Gun, 649-7113, Wakayama, Japan., Masuda K; Department of Orthopaedic Surgery, University of California-San Diego, 9500 Gilman Dr., MC0863, La Jolla, CA, 92093-0863, USA. komasuda@ucsd.edu.
Jazyk: angličtina
Zdroj: 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 [Eur Spine J] 2018 Apr; Vol. 27 (4), pp. 739-751. Date of Electronic Publication: 2018 Feb 19.
DOI: 10.1007/s00586-018-5488-1
Abstrakt: 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.
Databáze: MEDLINE
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