The catabolic effect of TNFa on bovine nucleus pulposus intervertebral disc cells and the restraining role of glucosamine sulfate in the TNFa-mediated up-regulation of MMP-3

Abstract

Glucosamine is an endogenous amino monosaccharide naturally occurring in the cartilage. We have recently shown that glucosamine sulfate promotes the biosynthesis of glycosaminoglycans in intervertebral disc cells. Here we assessed the role of glucosamine sulfate in the response of bovine nucleus pulposus cell monolayers to TNFa that constitutes an early signal of disc degeneration. TNFa was not found to affect nucleus pulposus cells' viability, while it resulted in a ∼2.5-fold increase of the intracellular ROS levels, a rapid transient phosphorylation of p38 MAPK and a ROS-dependent activation of JNKs. In addition, TNFa had a prominent inflammatory effect on nucleus pulposus cells by up-regulating MMP-3 expression that was reversed when inhibiting the kinase activity of p38 MAPK. Glucosamine sulfate also diminished the increased by TNFa MMP-3 mRNA levels, but this was unrelated to the p38 MAPK or ROS-mediated JNK activation. Even though the mode of action of glucosamine towards TNFa remains to be elucidated, to the best of our knowledge, this is the first report providing evidence for the protective role of glucosamine against this early mediator of disc degeneration that could support the potential usage of this molecule as a treatment for preventing disc degenerative disorders.