The pathophysiologic role of the protein kinase C? pathway in the intervertebral discs of rabbits and mice: in vitro, ex vivo, and in vivo studies.

ABSTRACT: Protein kinase C? (PKC?) activation has been shown to be a principal rate-limiting step in matrix-degrading enzyme production in human articular chondrocytes. The aim of this study was to assess the role of the PKC pathways, specifically PKC?, in intervertebral disc tissue homeostasis.Using in vitro, ex vivo, and in vivo techniques, we evaluated the pathophysiologic role of the PKC? pathway by examining 1) proteoglycan deposition, 2) matrix-degrading enzyme production and activity, 3) downstream signaling pathways regulated by PKC?, and 4) the effect on in vivo models of disc degeneration in genetically engineered PKC?-knockout mice.Studies of pathway-specific inhibitors revealed a vital role of the PKC?/MAPK (ERK, p38, JNK) axis and NF-?B in disc homeostasis. Accordingly, in an in vivo model of disc injury, PKC?-knockout mice were markedly resistant to disc degeneration.Suppression of the PKC? pathway may be beneficial in the prevention and/or treatment of disc degeneration. The results of this study provide evidence for a potential therapeutic role of pathway-specific inhibitors of the PKC? cascade in the future.

SUBMITTER: Ellman MB 

PROVIDER: S-EPMC3307815 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature