CHONDROCYTE ECTO-ENZYME PYROPHOSPHATE METABOLISM

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Research in the last decade has revealed that abnormally high intra-articular production of inorganic pyrophosphate (PPi) is an important metabolic defect in calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystal deposition arthropathies and possibly osteoarthritis. Cartilage has been identified as a probable source of excess articular PPi, and recent experiments have shown that the isolated chondrocyte, but not synovial derived cells, can account for all the PPi released from cartilage in vitro. Abnormalities in the activity of the PPi generating ecto-enzyme, nucleotide phyrophosphohydrolase (NPPH), correlate well with the observed abnomalities in synovial fluid PPi concentration. This may be of pathogenetic importance. A chondrocyte monolayer culture model of spontaneous extracellular PPi and NPPH elaboration which reproduces synovial fluid measurements of PPi and NPPH activity in human joints. This model furnish an ideal system in which to study the role of chondrocyte ecto-NPPH action in chondrocyte PPi elaboration. Chondrocyte NPPH will be purified and used to prepared rabbit antisera. An antibody could selectively block NPPH activity and therefore determine if extracellular PPi elaboration can be uncoupled from ecto-NPPH action. Additional experiments are proposed to determine the major metabolic source(s) of chondrocyte PPi and mechanisms of spontaneous elaboration of extracellular PPi and NPPH by chondrocytes.