title: Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.
abstract: In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.
mesh_terms: D002131:Calcium Pyrophosphate / Q000378:metabolism*; D002478:Cells, Cultured; D003460:Crystallization; D011756:Diphosphates / Q000032:analysis* / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010760:Phosphorus Metabolism Disorders / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D011755:Pyrophosphatases; C021895:nucleoside triphosphate pyrophosphatase; D002131:Calcium Pyrophosphate