Adenosine triphosphate pyrophosphohydrolase and neutral inorganic pyrophosphatase in pathologic joint fluids. Elevated pyrophosphohydrolase in calcium pyrophosphate dihydrate crystal deposition disease

Abstract

Adenosine triphosphate pyrophosphohydrolase (ATI'PPH) and neutral inorganic pyrophosphatase activities were assayed in synovial fluids (SF) from 37 patients with a variety of arthropathies. ATPPPH activity was detected in all fluids, but was highest in patients with chronic chondrocalcinosis; its activity in patients with osteoarthritis was higher than that in patients with rheumatoid arthritis, gout, or pseudogout. ATPPPH activity correlated positively with SF pyrophosphate concentration and negatively with SF white blood cell count. Pyrophosphatase activity did not correlate with diagnosis, pyrophosphate level, or white blood cell count.In virtually all arthropathies, inorganic pyrophosphate (PPi) concentration is higher in synovial fluid (SF) than in plasma, and the highest SF PPi levels are found in patients with calcium pyrophosphate dihydrate (CPPD) crystal, deposition disease (1-6). Maintenance of low levels of PPi in mammalian tissues has been attributed to ubiquitous pyrophosphatases, since: removal of this byproduct of multiple important synthetic reactions favors continuing synthesis (7).

Specificity of a porcine 127‐kd nucleotide pyrophosphohydrolase for articular tissues

“…PPi levels in joint fluid correlated positively with NTPPHase activity (19). Moreover, NTPPHase activity was increased in fluids from joints with CPPD crystal deposition (5,19). The concurrence of higher ATP levels and greater synovial fluid NTPPHase activity implies a more rapid rate of ATP release from The specificity of the 127-kd NTPPHase for cartilage and other joint tissues could potentially be useful as a marker of joint tissue metabolism if this molecule or its degradation products can be detected and quantified in serum or urine.…”

“…ATP levels were significantly (2-fold) greater in synovial fluids from joints with CPPD crystal deposits compared with fluids from osteoarthritis patients (4). PPi levels in joint fluid correlated positively with NTPPHase activity (19). Moreover, NTPPHase activity was increased in fluids from joints with CPPD crystal deposition (5,19).…”

Differential effects of aging on human chondrocyte responses to transforming growth factor-β: Increased pyrophosphate production and decreased cell proliferation

“…In addition, a 2-3-fold increase in intracellular PPi has been found in cartilage cells, fibroblasts, and lymphoblasts cultured from chondrocalcinosis patients (17)(18)(19). In support of this idea are results indicating that PPi, ATP (22), and NTPPPH (23) are elevated in the synovial fluid of patients with pseudogout compared with that from patients with other forms of arthritis or normal synovial fluid. Moreover, the presence of CPPD crystal deposition commonly complicates prior articular injury and is an adverse prognostic factor in osteoarthritis (OA) (1.…”

Extracellular nucleotide metabolism and signaling in the pathophysiology of articular cartilage

“…NPP1 and CILP/NTPPH were detected by Western blot in cell-free human synovial fluid (54). Synovial NTPPH activity varies with the diagnosis (activity in chronic chondrocalcinosis Ͼ activity in OA Ͼ activity in rheumatoid arthritis and gout) (108).…”