Panax notoginseng saponins attenuate intervertebral disc degeneration by reducing the end plate porosity in lumbar spinal instability mice

Abstract

Although painkillers could alleviate some of the symptoms, there are no drugs that really cope with the intervertebral disc degeneration (IDD) at present, so it is urgent to find a cure that could prevent or reverse the progression of IDD. During the development of IDD, the cartilaginous end plates (EPs) become hypertrophic and porous by the increase of osteoclast activities, which hinder the penetration of nutrition. The compositional and structural degeneration of the EP may cause both nutritional as well as mechanical impairment to the nucleus pulposus (NP) so that developing drugs that target the degenerating EP may be another option in addition to targeting the NP. In the lumbar spine instability mouse model, we found increased porosity in the cartilaginous EP, accompanied by the decrease in total intervertebral disc volume. Panax notoginseng saponins (PNS), a traditional Chinese patent drug with anti-osteoclastogenesis effect, could alleviate IDD by inhibiting aberrant osteoclast activation in the porous EP. Further in vitro experiment validated that PNS inhibit the receptor activator of nuclear factor kappa-Β ligand–induced osteoclast differentiation, while the transcriptional activation of PAX6 may be involved in the mechanism, which had been defined as an inhibitory transcription factor in osteoclastogenesis. These findings may provide a novel therapeutic strategy for IDD.