Molecular mechanism of basic calcium phosphate crystal-induced activation of human fibroblasts - Role of nuclear factor kappa B, activator protein 1,and protein kinase C

Synovial fluid basic calcium phosphate (BCP) crystals are markers of severe joint degeneration in osteoarthritis. BCP crystals cause mitogenesis of ar ticular cells and stimulate matrix metalloprotease production, thus promoti ng degradation of articular tissues. Previous work suggested that BCP cryst al-induced cell activation required intracellular crystal dissolution induc tion of proto-oncogene expression, and activation of signal transduction pa thways involving protein kinase C and mitogen-activated protein kinases. He re we further elucidate the mechanisms of BCP crystal-induced cell activati on as ECP crystals activate transcription factors nuclear factor KB and act ivator protein 1 in human fibroblasts. We confirm the role of protein kinas e C in BCP crystal-induced mitogenesis in human fibroblasts. In contrast, w e demonstrate that BCP crystals do not activate signal transduction pathway s involving protein tyrosine kinases or phosphatidylinositol S-kinase. Thes e data further define the mechanism of cell activation by BCP crystals and confirm its selectivity, an observation that may have therapeutic implicati ons.