2022, Vol. 26 ›› Issue (12): 1816-1821
Effect and mechanism of mechanical factors on intervertebral disc degeneration
Our previous study found that mechanical stimulation can affect many key proteins in the Wnt/β-catenin signaling pathway (including β-catenin and GSK-3β protein), but whether it regulates the Wnt/β-catenin signaling pathway in nucleus pulposus cells remains to be clarified.
To clarify the characteristics and effect of continuous loading pressure on intervertebral disc degeneration, and explore the mechanism of mechanical factors-mediated Wnt/β-catenin signaling pathway on intervertebral disc degeneration.
Seventy New Zealand white rabbits were selected to establish a rabbit spinal motion segment model, which were randomly divided into blank control group (0 kg), low pressure group (0.5 kg), medium pressure group (1 kg), and high pressure group (3 kg) according to the sustained loading pressure. Others were divided into control group by using optimal sustained loading pressure, activator group and inhibitor group by using Wnt/β-catenin specific activators (SB216763) and inhibitors (ICG001), for 3 consecutive days. Hematoxylin-eosin staining, DAB staining, western blot assay, and RT-PCR were used to observe the function of nucleus pulposus cells. The protocols were approved by Medical Ethics Committee of Wangjing Hospital, China Academy of Chinese Medical Sciences.
(1) The survival rate of nucleus pulposus cells was high under medium pressure (1 kg). Sustained loading pressure could induce intervertebral disc degeneration at 3 days. (2) Compared with the control group, the number of nucleus pulposus cells in the activator group was significantly increased; the cell morphology was regular, and the fibrous tissue and scar in the nucleus pulposus were not obvious. The expression levels of β-catenin and Aggrecan protein were higher and the experssion of GSK-3β protein was significantly decreased (P < 0.05). The expression levels of Aggrecan and Collagen II mRNA were significantly increased (P < 0.05). (3) Compared with the control group, the number of nucleus pulposus cells in the inhibitor group was significantly reduced; the cell morphology was fusiform, and the fibrous tissue and scar in the nucleus pulposus were more obvious; the expression levels of GSK-3β and β-catenin were not significantly different, but the expression of Aggrecan and Collagen II mRNA decreased significantly (P < 0.05). (4) It is concluded that sustained loading force regulates the process of intervertebral disc degeneration in nucleus pulposus cells by mediating Wnt/β-catenin signaling pathway.
lumbar disc herniation, intervertebral disc degeneration, continuous load pressure, nucleus pulposus cells, Wnt/β-catenin signaling pathway