Interleukin-17A Promotes Human Disc Degeneration by Inhibiting Autophagy Through the Activation of the Phosphatidylinositol 3-Kinase/Akt/Bcl2 Signaling Pathway.

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.

MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells.

Intervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. Here, the miRNA microassay assay identified 29 differentially expressed miRNAs in NP tissues from IDD patients compared with healthy controls. Following qRT-PCR validation, miR-21 expression was significantly upregulated in degenerated NP tissues, and showed a positive correlation with disc degeneration grade. Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.

Application of vascularized fibular graft for reconstruction and stabilization of multilevel cervical tuberculosis: A case report.

Multilevel cervical reconstruction and fusion after cervical tuberculosis has always been a challenge. The current implantation materials for cervical fusion, including titanium mesh, cage, and plate are limited by its inferior biological mechanical characteristics and the properties of the metallic material. This has led to the increased risk of recurrent infection after surgery. In addition, the unique nature of tuberculosis infection results in the low rate of cervical fusion and high risk of recurrence. This case report presents 1 patient who suffered from long segmental cervical tuberculosis and had reconstruction surgery using a vascularized fibula graft. The patient had successful graft incorporation 3 months postsurgery and was followed-up for 30 months. In this review, we detail the advantages of using vascularized fibular grafts and compare it with other types of grafts.