IL1-β and TNF-α induce changes in the nuclear polyphosphoinositide signalling system in osteoblasts similar to that occurring in patients with rheumatoid arthritis: an immunochemical and immunocytochemical study

摘要

Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint diseases that can lead to destruction of cartilage and structural changes in the subchondral bone. In this study we show by western blot and quantitative immunocytochemistry that nuclear phospholipase C β_1 (PLCβ_1) and phosphatidylinositol 4,5-bisphosphate (PIP_2), two key elements of the polyphosphoinositide signal transduction system that regulate different cellular processes, increase in primary osteoblast cultures of RA patients when compared with post-traumatic after fall (PT) patients, whilst those of OA are not significantly affected. Moreover, we demonstrate that these alterations could be induced in PT osteoblasts by proinflammatory cytokines IL-1β and TNF-α. This suggests that proinflammatory cytokines, highly produced by RA infiltrating mononuclear cells, can modulate the nuclear polyphosphoinositide signalling pathway of the osteoblasts involved in bone remodelling.