PKC-zeta expression is lower in osteoblasts from arthritic patients: IL1-beta and TNF-alpha induce a similar decrease in non-arthritic human osteoblasts

J Cell Biochem. 2008 Feb 1;103(2):547-55. doi: 10.1002/jcb.21424.

Abstract

Protein kinase C (PKC) is a family of enzymes detected in a diverse range of cell types where they regulate various cellular functions such as proliferation, differentiation, cytoskeletal remodelling, cytokine production, and receptor-mediated signal transduction. In this study we have analyzed the expression of 11 PKC isoforms (-alpha, -beta(I), -beta(II), -gamma, -delta, -eta, -theta, -epsilon, -zeta, -iota/lambda, and -micro) in osteoblasts from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in comparison with osteoblasts from post-traumatic (PT) patients. By Western blotting analysis, nine isoforms, -alpha, -beta(I), -beta(II), -delta, -theta, - epsilon, -zeta, - iota/lambda, and -micro, were detected in osteoblasts. In RA and OA patients, PKC -theta and -micro were greater expressed whereas PKC-epsilon and -zeta decreased when compared with normal cells. The subcellular distribution and quantitative differences were confirmed by immuno-electron microscopy. Furthermore, we demonstrated that treatment with the proinflammatory cytokines, IL-1beta and TNF-alpha, significantly decreased PKC-zeta expression in PT osteoblasts. This suggests that proinflammatory cytokines can modulate the expression of this PKC isoform in osteoblasts in a way which is similar to changes detected in arthritic patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured / drug effects
  • Cells, Cultured / enzymology
  • Enzyme Induction / drug effects
  • Female
  • Femur Head / enzymology
  • Femur Head / ultrastructure
  • Hip Injuries / pathology
  • Humans
  • Interleukin-1beta / pharmacology*
  • Isoenzymes / analysis
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Osteoarthritis / enzymology*
  • Osteoarthritis / pathology
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology*
  • Osteoblasts / ultrastructure
  • Protein Kinase C / analysis
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / deficiency*
  • Protein Kinase C / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Interleukin-1beta
  • Isoenzymes
  • Tumor Necrosis Factor-alpha
  • protein kinase C zeta
  • Protein Kinase C