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
Gm. Mccarthy et al., 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, J BIOL CHEM, 273(52), 1998, pp. 35161-35169
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.