17β-Estradiol alleviates intervertebral disc degeneration by inhibiting NF-κB signal pathway

Aim: To investigate the effect of 17 beta-Estradiol (E2) on intervertebral disc degeneration (IVDD) and the related mechanism. Materials and methods: Immunohistochemistry was used to detect the expression of estrogen receptor beta (ER beta) within intervertebral discs of humans and rats. After that, rat IVDD model was established by needle puncture and bilateral ovariectomy. Then, the serum E2 level was detected by enzyme linked immunosorbent assay, and the degree of IVDD was evaluated by X-ray, magnetic resonance imaging, hematoxylin and eosin staining, and Safranin O-Fast Green staining. Finally, we used immunohistochemistry and immunofluorescence staining to determine the effect of E2 on nuclear factor kappa-B (NF-kappa B) signal pathway both in vivo and in vitro. Key findings: We identified that IVDD was associated with lower levels of ER beta and ER beta levels were inversely correlated with IVDD. The histological staining and radiological results showed that E2 supplement could alleviate IVDD progression. Additionally, immunohistochemistry staining demonstrated that E2 could inhibit nucleus pulposus cell (NPC) apoptosis, matrix metalloproteinases (MMPs) synthesis, and degradation of extracellular matrix (ECM) by inhibiting the activation of NF-kappa B signal pathway. Furthermore, immunofluorescence staining showed that the above effects of E2 on the NF-kappa B signal pathway could be blocked by the estrogen receptor antagonist IC1182780 in vitro. Finally, inhibition of NF-kappa B signal pathway by BAY11-7082 could reduce MMPs synthesis and ECM degradation of NPCs. Significance: Collectively, these findings indicated that E2 could effectively ameliorate IVDD by inhibiting NPC apoptosis via inhibition of NF-kappa B signal pathway.

Automated summary

The study discovered that 17 beta-Estradiol (E2) can ameliorate intervertebral disc degeneration (IVDD) by inhibiting nucleus pulposus cell apoptosis, and this effect is mediated through regulation of the NF-kappa B signal pathway.