Advanced Glycation End Products Induce Caudal Disc Degeneration in Ovariectomized Female Rats

Preclinical animal models are indispensable for the development of new therapeutic strategies and the study of the pathological mechanisms of intervertebral disc (IVD) degeneration (IVDD). This study aims to develop a reliable and reproducible rat model of IVDD by injecting advanced glycation end products (AGEs) into the IVD of ovariectomized rats.

Twenty-eight female Sprague-Dawley rats were allocated into the 31G needle group, vehicle group, 0.5 μg AGEs group, 1 μg AGEs group, 2 μg AGEs group, 4 μg AGEs group, and non-ovariectomy group (n = 4). The coccygeal discs of the 31G needle group were punctured only, while the coccygeal discs of the vehicle group were injected with 1 μL PBS. The coccygeal discs of the AGEs groups underwent injection of AGEs at 0.5, 1, 2, and 4 μg, respectively. The coccygeal discs of the non-ovariectomy group were injected with 2 μg AGEs. Rats in all groups, except for the non-ovariectomy group, underwent bilateral ovariectomy. Two weeks later, the rat caudal models were evaluated using radiological examination, histological staining, and immunohistochemistry (IHC).

No signs of IVDD were found by radiological imaging, histology, or IHC in the 31G needle group or the vehicle group. By contrast, in the 0.5, 1, 2, and 4 μg AGEs groups, caudal IVDD was successfully established and the IVDD severity is increasing in a dose-dependent manner. Compared with the 2 μg AGEs group, rats in the non-ovariectomized group showed less IVDD, indicating the protective effect of endogenous estrogen on degenerative IVD.

A single injection of AGEs to caudal discs can cause reliable and reproducible IVDD in ovariectomized female rats. Additionally, the endogenous estrogen might have a protective effect on the IVD to mitigate the degeneration.