Growth differentiation factor‐6 attenuates inflammatory and pain‐related factors and degenerated disc‐induced pain behaviors in rat model
Autor: | Jianru Wang, Hui Liu, Xianfa Du, Ashish D. Diwan, Zhaomin Zheng, Zemin Li, Haitao Cui, Jian Zhang, Haowen Cui, Fan Chen |
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Rok vydání: | 2020 |
Předmět: |
Male
Pathology medicine.medical_specialty 0206 medical engineering Pain Inflammation Intervertebral Disc Degeneration 02 engineering and technology Growth Differentiation Factor 6 Matrix metalloproteinase Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Dorsal root ganglion Animals Medicine Orthopedics and Sports Medicine 030203 arthritis & rheumatology business.industry Interleukin Intervertebral disc Magnetic Resonance Imaging 020601 biomedical engineering Rats medicine.anatomical_structure Calcitonin Cytokines Resistin Tumor necrosis factor alpha medicine.symptom business |
Zdroj: | Journal of Orthopaedic Research. 39:959-970 |
ISSN: | 1554-527X 0736-0266 |
Popis: | Previous studies have indicated that growth differentiation factor 6 (GDF6) is a potential candidate for intervertebral disc (IVD) degeneration (IDD) treatment. Here, we investigated the effect of GDF6 on IDD by examining changes in disc structure and the expression of inflammatory and pain-related factors. A rat posterior disc puncture model of single segments and three consecutive segments was constructed, and GDF6 or phosphate-buffered solution was administered via intradiscal injection 1 or 2 weeks after surgery. Magnetic resonance imaging showed a clear degeneration signal in the punctured disc, which was inhibited by GDF6. Histological staining revealed that GDF6 did not significantly improve the structure of IVDs in rats 8 weeks after puncture surgery, but it had an inhibitory effect on expression of the tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in the IVD. Furthermore, GDF6 was found to protect the morphology and structure of the IVD 32 weeks after surgery. Mechanical and thermal hyperalgesia tests suggested that GDF6 injection can significantly improve mechanical and thermal-stimulated pain behavior in rats and inhibit the expression of inflammatory factors TNF-α and IL-1β and the pain factor calcitonin gene-related peptide in the dorsal root ganglion. A rat protein array test indicated that GDF6 could reduce the expression of cytokines IL-6, intercellular cell adhesion molecule-1, matrix metalloproteinase-13, IL-1β, and TNF-α and increase the expression of tissue inhibitor of metalloproteinases 1, Transforming growth factor-beta 2, IL-10, and resistin in a TNF-α-induced IDD cell model. Thus, our study demonstrates that GDF6 can improve the structure of the IVD, inhibit the expression of inflammatory and pain-related factors, and improve pain behavior in rats. Clinical Significance: To establish further preclinical research and clinical trials, comprehensive data are needed to validate the regenerative properties of GDF6. Ideally, a regenerative agent should also be able to relieve discogenic pain, achieving the best clinical outcomes. |
Databáze: | OpenAIRE |
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