In the past three years, there has been considerable progress in delineatin
g the mechanism of calcium-containing crystal-induced cell activation: (1)
the identification of Ca2+ influx and p42/44 mitogen-activated protein kina
se activation as the signal transduction pathways; (2) induction of nuclear
transcription factors of cyclic adenosine monophosphate (cAMP) response el
ement binding protein, activator protein-1, and nuclear factor kappa B; (3)
the differential role of crystal endocytosis and dissolution in crystal-in
duced metalloproteinase synthesis and mitogenesis; (4) crystal upregulation
of matrix metalloproteinases, including MMP-13 but downregulation of tissu
e inhibitor of metalloproteinase-1 and -2, thus magnifying the degenerative
effect of crystals. Phosphocitrate, a specific inhibitor of biologic effec
t of calcium crystals, reverses the degenerative effects of crystals, Curr
Opin Rheumatol 2000, 12:223-227 (C) 2000 Lippincott Williams & Wilkins, Inc
.