title: The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: in vitro, ex vivo, and in vivo studies.
abstract: OBJECTIVE
  Protein kinase Cδ (PKCδ) 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 PKCδ, in intervertebral disc tissue homeostasis.
  
  
  METHODS
  Using in vitro, ex vivo, and in vivo techniques, we evaluated the pathophysiologic role of the PKCδ pathway by examining 1) proteoglycan deposition, 2) matrix-degrading enzyme production and activity, 3) downstream signaling pathways regulated by PKCδ, and 4) the effect on in vivo models of disc degeneration in genetically engineered PKCδ-knockout mice.
  
  
  RESULTS
  Studies of pathway-specific inhibitors revealed a vital role of the PKCδ/MAPK (ERK, p38, JNK) axis and NF-κB in disc homeostasis. Accordingly, in an in vivo model of disc injury, PKCδ-knockout mice were markedly resistant to disc degeneration.
  
  
  CONCLUSIONS
  Suppression of the PKCδ 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 PKCδ cascade in the future.
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ellman
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kroin
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Dongyao
authors.initials: D
authors.lastname: Yan
authors.forename: Doug D
authors.initials: DD
authors.lastname: Buechter
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Morgan
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D007403:Intervertebral Disc / Q000187:drug effects / Q000201:enzymology*; D055959:Intervertebral Disc Degeneration / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D011509:Proteoglycans; D051745:Protein Kinase C-delta