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1.
World Neurosurg ; 143: e215-e223, 2020 11.
Article in English | MEDLINE | ID: mdl-32712400

ABSTRACT

BACKGROUND: Previous studies have suggested that interleukin (IL)-17A is a key factor that contributes to intervertebral disc degeneration (IDD), whereas autophagy has been shown to be a protective mechanism in IDD. However, the relationship between IL-17A and autophagy in IDD remains to be fully elucidated. This study sought to evaluate the association between IL-17 and autophagy and the potential mechanism through which IL-17A affects autophagy in IDD. METHODS: Intervertebral disc specimens were collected from 10 patients with lumbar disc herniation. Human degenerated nucleus pulposus (NP) cells were cultured in the presence or absence of IL-17A treatment. Western blot and monodansylcadaverine staining were used to measure autophagy levels in human degenerated NP cells. Subsequently, phosphatidylinositol 3-kinase (PI3K)/Akt/Bcl-2 pathway inhibitors were used to reveal the potential mechanism. RESULTS: IL-17A treatment inhibited the autophagic activity in human NP cells in a time- and dose-dependent manner. Moreover, monodansylcadaverine staining showed that cells treated with IL-17A had significantly fewer changes in their autophagic vacuoles compared with control-treated cells. After IL-17A treatment, expression levels of PI3K, p-Akt, and Bcl-2 in NP cells were significantly increased. Further assays with PI3K/Akt/Bcl-2 inhibitors revealed that IL-17A suppressed autophagy in NP cells by activating the PI3K/Akt/Bcl-2 signaling pathway. CONCLUSIONS: These data suggest that IL-17A promotes IDD by inhibiting autophagy through activation of the PI3K/Akt/Bcl-2 signaling pathway and may offer new insights for targeted therapy of this disease.


Subject(s)
Autophagy/immunology , Interleukin-17/immunology , Intervertebral Disc Degeneration/immunology , Nucleus Pulposus/immunology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Aged , Autophagy/drug effects , Cells, Cultured , Female , Humans , Interleukin-17/pharmacology , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Displacement , Male , Middle Aged , Nucleus Pulposus/cytology , Nucleus Pulposus/metabolism , Phosphatidylinositol 3-Kinases/drug effects , Phosphatidylinositol 3-Kinases/pharmacology , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/drug effects , Signal Transduction
2.
J Surg Res ; 181(2): e65-74, 2013 May.
Article in English | MEDLINE | ID: mdl-22878152

ABSTRACT

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.


Subject(s)
Disease Models, Animal , Intervertebral Disc Degeneration , Intervertebral Disc/surgery , Punctures/methods , Rabbits , Radiography, Interventional , Tomography, X-Ray Computed , Animals , Biomarkers/metabolism , Glycosaminoglycans/metabolism , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Magnetic Resonance Imaging , Needles , Punctures/instrumentation
3.
Orthop Surg ; 1(3): 231-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-22009848

ABSTRACT

OBJECTIVE: To evaluate the biocompatibility of a new kind of prosthetic nucleus: a pectin/polyvinyl alcohol composite (CoPP) hydrogel. METHODS: According to Chinese national standard GB/-T16886 documents, the toxicity of the CoPP prosthetic nucleus material was examined by cytotoxicity, sensitization, Ames, mice marrow micronucleus, chromosome aberration test of mammalian cell and implantation tests. RESULTS: Cell growth was similar in the CoPP culture and control groups. No significant difference was found between the CoPP culture and control groups at each time point (P > 0.05). The cell proliferation rate was greater than 100%. In accordance with the relationship between cytotoxicity to proliferation rate, it was confirmed that the cytotoxicity of CoPP was 0 grade. Mice had no allergic reaction when injected with an extract of CoPP. A reverse mutation test with Salmonella typhimurium showed that no significant effect on the number of histidine revertants of TA97, TA98, TA100 and TA102 strains after CoPP was added. The micronucleus rate in bone marrow cells was less than 5%; there was no significant difference compared with the negative control group (P > 0.05). The rate of chromosome aberration was less than 5%; no significant difference was found between the CoPP culture and the control groups. All experimental animal wounds achieved primary healing without exudation, infection or sinus formation. On macroscopic observation, no abscess or hematoma formed at the implantation site. CONCLUSION: The CoPP prosthetic nucleus has good biocompatibility and can potentially be used as an implant material.


Subject(s)
Biocompatible Materials , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Implants, Experimental , Intervertebral Disc/surgery , Pectins/chemistry , Polyvinyl Alcohol/chemistry , Animals , Cells, Cultured , Female , Guinea Pigs , Intervertebral Disc/cytology , Male , Materials Testing/methods , Mice
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