Hyperglycemia in the Diabetes mellitus (DM) patients is a potential etiology of disc degeneration. 17β-estradiol (17β-E₂) supplementation plays an anti-diabetic role in DM patients.

This study was aimed to investigate the role and mechanism of 17β-E₂ in regulating nucleus pulposus (NP) cell apoptosis and NP matrix production under a high glucose condition.

Rat NP cells were cultured in medium with a high glucose concentration (0.2 M). 17β-E₂ was added into the culture medium to investigate its protective effects. The ERβ inhibitor PHTPP and ERβ activator ERB041 were used to investigate the effects of ERβ. NP cell apoptosis was analyzed by flow cytometry and expression of apoptosis-related molecules. NP matrix production was evaluated by expression of matrix macromolecules. Additionally, intracellular reactive oxygen species (ROS) content was also detected.

Compared with the control NP cells, 17β-E₂ decreased NP cell apoptosis ratio, down-regulated gene expression of Bax and caspase-3, up-regulated gene expression of Bcl-2, increased protein expression of cleaved PARP and cleaved caspase-3, and increased expression of matrix molecules (aggrecan and collagen II). Moreover, 17β-E₂ decreased ROS content. Further analysis showed that ERβ inhibition partly reversed these effects of 17β-E₂ whereas ERβ activation further promoted its effects.

17β-E₂/ERβ interaction attenuates apoptosis and promotes matrix biosynthesis of NP cells through alleviating oxidative damage under a high glucose condition. This study provides new knowledge on strategies for retarding disc degeneration.