The functional expression of connexin 43 in articular chondrocytes is increased by interleukin 1β: Evidence for a Ca 2+ ‐dependent mechanism

Abstract

Cell‐to‐cell interactions and gap junctions‐dependent communication are crucially involved in chondrogenic differentiation, while in adult articular cartilage direct intercellular communication occurs mainly among chondrocytes facing the outer cartilage layer. Chondrocytes extracted from adult articular cartilage and grown in primary culture express connexin 43 and form functional gap junctions capable of sustaining the propagation of intercellular Ca²⁺ waves. Degradation of articular cartilage is a characteristic feature of arthritic diseases and is associated to increased levels of interleukin‐1 (IL‐1) in the synovial fluid. We have examined the effects of IL‐1 on gap junctional communication in cultured rabbit articular chondrocytes. Incubation with IL‐1 potentiated the transmission of intercellular Ca²⁺ waves and the intercellular transfer of Lucifer yellow. The stimulatory effect was accompanied by a dose‐dependent increase in the expression of connexin 43 and by an enhanced connexin 43 immunostaining at sites of cell‐to‐cell contact. IL‐1 stimulation induced a dose‐dependent increase of cytosolic Ca²⁺ and activates protein tyrosine phosphorylation. IL‐1‐dependent up‐regulation of connexin 43 could be prevented by intracellular Ca²⁺ chelation, but not by inhibitors of protein tyrosine kinases, suggesting a crucial role of cytosolic Ca²⁺ in regulating the expression of connexin 43. IL‐1 is one of the most potent cytokines that promotes cartilage catabolism: its modulation of intercellular communication represents a novel mechanism by which proinflammatory mediators regulate the activity of cartilage cells.