PKC-ζ expression is lower in osteoblasts from arthritic patients: IL1-β and TNF-α induce a similar decrease in non-arthritic human osteoblasts

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 (-α, -βI, -βII, -γ, -δ, -η,-θ,-ε, -ζ, -ι/λ, and -μ) 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, -α, -βI, -βII, -δ, -θ, -ε, -ζ, -ι/λ, and -μ, were detected in osteoblasts. In RA and OA patients, PKC -θ and -μ were greater expressed whereas PKC-ε and -ζ 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-1β and TNF-α, significantly decreased PKC-ζ 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. © 2007 Wiley-Liss, Inc.