Calcium phosphate particle induction of metalloproteinase and mitogenesis: effect of particle sizes.
Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals [hydroxyapatite (HA), octacalcium phosphate, tricalcium phosphate] are common in osteoarthritis knee effusions, and are often associated with low-grade synovial proliferation and inflammation. Calcium-containing crystals including HA, are known to have a number of biologic effects on culture cells such induction of mitogenesis, stimulation of Prostaglandin E2 (PGE2) production via the phospholipase A2/cyclo-oxygenase pathway, activation of phospholipase C and inositol phospholipid hydrolysis, induction of metalloproteinase synthesis and induction of proto-oncogenes (c-fos and c-myc). While endocytosis of HA particles is prerequisite of the mitogenic effect of calcium-containing crystals in fibroblasts, it is not known whether endocytosis is required for crystal-induced metalloproteinase synthesis. In the present series of experiments, we examine the effect of three different sizes (106, 46, and 17 microns mean diameters) well-characterized spherical HA particles on the induction of mitogenesis and metalloproteinase synthesis on human fibroblasts. We showed that endocytosis is required for HA particles to induce synthesis of metalloproteinases.
Cheung
H S
HS
Division of Rheumatology, Medical College of Wisconsin, Milwaukee 53226, USA.
Devine
T R
TR
Hubbard
W
W
D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D017364:Collagenases / Q000032:analysis; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts; D006801:Humans; D008666:Metalloendopeptidases / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D010316:Particle Size
D001672:Biocompatible Materials; D017886:Durapatite; D017364:Collagenases; D008666:Metalloendopeptidases