Enzymatic Behavior of Condoliase in Porcine Nucleus Pulposus: Ex Vivo and In Vitro Assessment

Abstract

Background

Condoliase is a treatment for lumbar disc herniation. This enzyme exerts its medicinal effects by digesting chondroitin sulfate (CS), which is abundant in the nucleus pulposus. However, the behavior of administered condoliase in the nucleus pulposus is not clear. Because the purpose of this study is to understand the mechanism of enzyme action, we evaluated the properties of condoliase in the nucleus pulposus.

Methods

The following were evaluated: (1) The diffusibility of fluorescein labeled condoliase injected into isolated porcine nucleus pulposus. (2) The time dependence of condoliase activity in porcine nucleus pulposus or CS solution. (3) The morphology of the enzyme-treated nucleus pulposus tissue was characterized using scanning electron microscopy.

Results

After injection into the nucleus pulposus, condoliase was difficult to diffuse spontaneously, and the rate of CS-disaccharides production was significantly increased up to a peak at 24 h and decreased thereafter. Not all of the CS in the nucleus pulposus was digested by condoliase. These results suggested that condoliase digested CS locally without causing its spontaneous diffusion within the nucleus pulposus. Moreover, condoliase did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.

Conclusions

We demonstrated that condoliase is retained in the nucleus pulposus and exerts its pharmacological effects by locally degrading CS without degrading collagen fibers. The results obtained in this study can be useful in predicting the mechanism of the pharmacological action of condoliase in clinical practice.