Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration

Background: Intervertebral disc degeneration is a complex disease with high prevalence. It suggests that cell death, senescence, and extracellular matrix degradation are involved in the pathogenesis. Alpha-1 antitrypsin (AAT), a serine protease inhibitor, was previously correlated with inflammation-related diseases. However, its function on intervertebral disc degeneration remains unclear. Methods: A latex-enhanced immunoturbidimetric assay measured the serum level of AAT. Real-time polymerase chain reaction (RT-qPCR) and western blot were used to testify the expression of RNA and proteins related to cell apoptosis and the Wnt/beta-catenin pathway. The animal model for intervertebral disc degeneration was built by disc puncture. The degeneration grades were analyzed by safranin o staining. Results: We showed that alpha-1 antitrypsin could ameliorate intervertebral disc degeneration in vitro and in vivo. We also found that the serum alpha-1 antitrypsin level in Intervertebral disc degeneration patients is negative related to the severity of intervertebral disc degeneration. Moreover, alpha-1 antitrypsin was also showed to suppress tumor necrosis factor-alpha (TNF-alpha) induced WNT/beta-catenin signaling pathway activation in human nucleus pulposus cells. Conclusions: Our study provides evidence for AAT to serve as a potential therapeutic reagent for the treatment of intervertebral disc degeneration.