Phagocytosis of Hydroxyapatite or Calcium Pyrophosphate Dihydrate Crystals by Rabbit Articular Chondrocytes Stimulates Release of Collagenase,Neutral Protease,and Prostaglandins E 2 and F 2α

Abstract

Synthetic hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) microcrystals are phagocytosed by rabbit articular-cartilage chondrocytes in primary culture. The ingestion of crystals greatly stimulated the release of collagenase, neutral protease, and prostaglandins E₂ and F_2α into the ambient medium. Lactate dehydrogenase was not released by either crystal despite electron microscopic evidence of cell damage by HA crystals (partial loss of phagolysosomal membrane and increased myelin figures). HA, but not CPPD crystals, stimulated release of/3-glucuronidase. HA crystal concentrations from 50 to 200 μg ml^–1 induced a dose-dependent release of collagenase and of extracellular protein. Both phagocytosis and collagenase release were greatly attenuated when HA crystals were added to the chondrocyte monolayers in the absence of serum. As HA and CPPD crystals have been identified in human articular cartilage in association with degenerative changes, it is possible that the cell-crystal interaction described here may be pathogenetically important.