No abstract

One abnormality in calcium pyrophosphate deposition disease (CPDD) which fosters consistently high synovial fluid pyrophosphate ion (PPi) and large accumulations of calcium pyrophosphate dihydrate crystals (Ca pyrophosphate) might be an aberration in chondrocytes involving elaboration of PPi and failure of its hydrolysis within cartilage matrix. Exploration of this hypothesis required further information on the phosphohydrolases in relevant human articular cartilages. Triton X-100 extracts of whole homogenized cartilage from 18 patients with primary osteoarthritis (OA), 10 patients with CPDD and secondary OA, as well as 6 "normal" subjects were partially purified by DE-52 chromatography and eluates studied for phosphohydrolase activity in a variety of substrates, inhibitors, and environmental conditions. Almost all the protein as well as crude alkaline phosphatase and pyrophosphatase activities were clustered in peaks designated I and 11.From the Arthritis Divisions, Departments of Medicine, University of Toronto, Ontario, Canada, University of Miami, Florida, University of Pennsylvania, Philadelphia, and the University of Michigan. AM Arbor.Findings in CPDD cartilage not observed in OA controls were: 1) consistent alkaline phosphatase activity in the void volume of DE-52 columns, 2) high levels of Snucleotidase activity, 3) abundant generation of PPi by CPDD cartilage during in vitro incubation of cartilage extract fractions with ATP. This enzymatic behavior is likely to bear a regulatory relationship to PPi production by chondrocytes in CPDD.Deposition in articular cartilage of calcium pyrophosphate dihydrate crystals (Ca pyrophosphate) in middle-aged or elderly humans is productive of multiple clinical manifestations collectively defined as calcium pyrophosphate deposition disease (CPDD). A prominent secondary manifestation of CPDD is osteoarthritis (OA) (1).No systemic biochemical abnormality has yet been uncovered in CPDD, but consistently found is a substantial elevation of pyrophosphate ion (PPi) concentration in synovial fluid. Only rarely is there Ca pyrophosphate deposition in a joint or synovial fluid without evidence of deposition in cartilage (1). The ki- Because primary OA, like CPDD, was associated with elevated synovial fluid PPi levels (5), we studied OA cartilage for ppi production. It was shown that fresh human OA cartilage elaborated PPi ion into surrounding culture medium during incubation in shortterm organ culture. ppi accumulated in the medium as a function of time in contrast to multiple negative control cartilages (6). Rabbit growth cartilage also elaboform September 18, 1980.