Objective. To investigate cellular signaling mechanisms that influence chon
drocyte production of inorganic pyrophosphate (PPI), which promotes calcium
pyrophosphate dihydrate (CPPD) crystal deposition.
Methods. Articular chondrocyte and cartilage cultures were stimulated with
protein kinase C (PKC) activator and adenyl cyclase activator. Generation o
f extracellular PPi was measured.
Results. Adenyl cyclase activation resulted in diminished pyrophosphate gen
eration. PKC activation stimulated pyrophosphate elaboration.
Conclusion. Two signaling pathways, cAMP and PKC, modulate generation of ex
tracellular pyrophosphate by cartilage and chondrocytes. They are novel tar
gets for potentially diminishing extracellular pyrophosphate elaboration th
at leads to CPPD crystal deposition.