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PubMed2005

Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage.

Physiologic levels of extracellular PPi, which suppresses hydroxyapatite crystal growth, must be maintained by articular chondrocytes and resident cells in many othee tissues in order to prevent pathologic calcification. However, extracellular PPi rises in articular cartilage in direct association with aging. Matrix supersaturation with PPi stimulates chondrocalcinosis manifesting as calcium pyrophosphate dihydrate (CPPD) crystal deposition. Extracellular PPi levels are normally held in check by balances in PPi generation by nucleotide pyrophosphatase phosphodiesterase (NPP/NTPPPH) activity relative to PPi degradation by pyrophosphatases, by balance effects of cytokines and growth factors, and by transport of PPi from the cell interior involving the multiple-pass transmembrane protein ANK. But these mechanisms become dysrgulated in aging and osteoarthritic (OA) cartilage and extracellular PPi excess supervenes, mediated in large part by upregulated NPP1 and ANK expression in articular cartilage. Conversely, NPP1 and ANK deficiency states were recently linked to phenotypically similar forms of spontaneous soft tissue calcification with hydroxyapatite (HA). Here, we focus on recent advances in understanding of PPi metabolism and NPP1 and ANK function pertinent to the pathogenesis of pathologi matrix calcification in articular cartilage.

Animals↗

PubMed2004

[Jaccoud arthropathy and pyrophosphate arthropathy: a rare association].

Jaccoud's arthropathy (JA) is a chronic deformity affecting hands and feet, which are voluntarily correctable by the patients. JA was usually reported in association with rheumatic fever and systemic lupus erythematosus. We describe an exceptional association between a pyrophosphate arthropathy and JA of the hands. It is a 48-year-old woman, having a 13 years history of polyarthritis involving shoulders, elbows, hips and knees, and 4 years after, a progressive unlar deviation of the fingers of the hands. Calcium pyrophosphate dihydrate crystals were identified in the synovial knee biopsy. Hands x-rays as RMI don't identify erosions and confirmed the JA.

Arthritis↗

PubMed1991

Two cases of acute pseudogout attack following parathyroidectomy.

Two cases of acute attack of pseudogout associated with primary hyperparathyroidism are reported. Case 1 suffered from acute pain and swelling of the right ankle and dorsal of the right foot. Case 2 suffered from unknown fever and pain of the bilateral jaw, shoulder, elbow, wrist and knee joints. Postoperative radiological studies revealed the association of chondrocalcinosis in both cases. Synovial fluid in case 2 was aspirated and analyzed for calcium pyrophosphate dihydrate crystal by microscopic examination.

Acute Disease↗

PubMed2006

Pseudogout attack induced during etidronate disodium therapy.

We report the first case of pseudogout attack in the distal interphalangeal (DIP) joints during etidronate disodium therapy. A 64-year-old woman had intermittent administration of etidronate disodium (Didronel; Sumitomo, Osaka, Japan) alone because of osteoporosis. Each cycle consisted of a daily dose of 200 mg for 2 weeks, repeating every 12 weeks. Two weeks after completing the third cycle, severe pain and swelling occurred in the DIP joints of the right middle, ring, and left ring finger; and skin ulcer formation was observed on the dorsal side of the DIP joints of the right middle and ring fingers as well as the left ring finger. Because monoclinic calcium pyrophosphate crystals were detected in the synovial fluid from the DIP joints of the right middle finger, we diagnosed these symptoms as induced by pseudogout attack. Oral loxoprofen sodium at a daily dose of 180 mg resulted in rapid symptom resolution. A decrease in function of calcium metabolism in elderly persons has been reported to be a cause of pseudogout attack. On the other hand, distal interphalangeal joint arthritis presenting as Heberden's nodes is a common condition in elderly patients. Therefore, pseudogout attack should be considered as an adverse drug reaction when administering bisphosphonate in elderly patients with Heberden's nodes.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Acute arthritis after intra-articular hyaluronate injection: onset of effusions without crystal.

Side effects of intra-articular hyaluronate injection include aseptic acute arthritis, which develops within hours after injection. Based on standard crystal analysis, calcium crystal shedding has been postulated to explain this complication. However, it is not known whether apatite crystals or low amounts of calcium pyrophosphate dihydrate (CPPD) crystals are also involved as to determine this requires a complete synovial fluid (SF) analysis. Two cases of such an acute arthritis are reported in patients after receiving a second Hylan GF-20 intra-articular injection. The SF did not contain CPPD, monosodium urate, or calcium apatite microcrystals as examined by microscopic analysis (using a compensated polarised light microscope) after alizarin red staining. Further studies are required to investigate possible direct proinflammatory effects of hyaluronic acid degradation products.

Acute Disease↗

PubMed1980

Identification of an arginine important for enzymatic activity within the covalent structure of yeast inorganic pyrophosphatase.

Previously we presented evidence for an essential arginine involved in binding inorganic pyrophosphate during catalysis by yeast inorganic pyrophosphatase [Cooperman, B. S., & Chiu, N. Y. (1973b) Biochemistry 12, 1676]. In the present work we show this residue to be arginine-77. Arginine-77 reacts with [14C]phenylgloxal considerably faster than the other five phenylglyoxal is selectively blocked in the presence of the competitive inhibitor calcium pyrophosphate. Our procedure leading to the identification of Arg-77 utilizes the following steps: CNBr cleavage, digestion with Staphylococcus aureus V8 protease and with pepsin, and peptide mapping. All of these steps are performed below pH 5, a restriction imposed by the lability of the phenylglyoxal-arginine adduct at neutral pH. In related work, we find the model compound N alpha-acetyl(diphenylglyoxal)arginine to hydrolyze 10 times more slowly at pH 4 than at pH 7. The high yields of derivatized peptides obtained in this work suggest the potential general utility of our procedure for locating arginine residues derivatized with phenylglyoxal within the covalent structure of proteins.

Amino Acid Sequence↗

PubMed1975

An office technique for identifying crystal in synovial fluid.

Crystal identification is made with a polarizing, color-compensated light microscope. Most microscopes can be easily and inexpensively adapted for crystal identification. The color compensator allows differentiation between the monosodium urate crystals of gout and the crystals of pseudogout, or calcium pyrophosphate deposition disease. All synovial fluid specimens should be examined. The observation of phagocytosis of crystals establishes that they are the etiologic agent responsible for an ongoing acute attack of arthritis.

Betamethasone↗

PubMed1978

The interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast.

The interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast was investigated by measurement of their effect on the protein fluorescence. Fluorescence titrations of the native enzyme with uranyl nitrate show that there is a specific binding of uranyl ions to the enzyme. It was deduced that each subunit of the enzyme binds one uranyl ion. The binding constant was estimated to be in the order of 10(7) M-1. The enzyme which contains a small number of chemically modified carboxyl groups was not able to bind uranyl ions specifically. The modification of carboxyl groups was carried out by use of a water soluble carbodiimide and the nucleophilic reagent N-(2,4-dinitro-phenyl)-hexamethylenediamine. The substrate analogue calcium pyrophosphate displaced the uranyl ions from their binding sites at the enzyme. From the results it is concluded that carboxyl groups of the active site are the ligands for the binding of uranyl ions.

Calcium↗

PubMed1996

Tophus-like, conglomerated, crystalline calcification of the sclera.

The clinical history and the pathohistological findings of a peculiar form of multifocal scleral calcification in 3 globes of 2 patients are described. It consisted of globular drusen of rod-like crystals, fusing into large, tophus-like conglomerates. The crystals consisted of monoclinic and triclinic calcium pyrophosphate. The deposits can be interpreted therefore as scleral pseudogout. They were combined in places with a diffuse, idiopathic inner scleral calcification. The pathogenesis of these mineralizations is unclear. No signs of a dystrophic calcification were present. One patient, suffering from Alport's syndrome, had been normocalcemic for the last 16 years after renal transplantation, and no disturbed calcium metabolism was known in the second case.

Adult↗

PubMed1975

High synovial fluid white blood cell counts in pseudogout; Possible confusion with septic arthritis.

During a 12-month period, we have treated five patients with acute inflammatory arthritis and synovial fluid leukocyte counts of 65,000 to 100,00/cu mm with 93% to 100% polymorphonuclear cells, calcium pyrophosphate dihydrate crystals in the synovial fluid, and negative cultures. Four of these five were origingally treated for septic joints. We would like to emphasize this relatively uncommon, but important manifestation of pseudogout.

Arthritis, Infectious↗

PubMed1984

Prevalence of periarticular calcifications in pyrophosphate arthropathy and their relation to nodal osteoarthrosis.

X-rays of the shoulder, hand, and knee joints from 30 patients with pyrophosphate arthropathy (PA) and 30 age and sex matched control subjects were examined for periarticular, dense, homogeneous calcifications considered to be apatite deposits. They were found in 30% of the patients with PA compared with 3.3% of the controls. In addition in the PA group the incidence of Heberden's nodes was significantly increased in cases with periarticular calcifications, implying that mixed (calcium pyrophosphate dihydrate + apatite) crystal deposition disease could be related to nodal osteoarthrosis.

Adult↗

PubMedDate not supplied

Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles.

The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates.

Adenine Nucleotides↗

PubMed2001

Iron(III)-mediated intra-articular crystal deposition in arthritis: a therapeutic role for iron chelators.

Crystal deposition in arthritic diseases has attracted much interest. Many reports have established the presence of calcium pyrophosphate (CPPD), hydroxyapatite (HAP) and urate crystals throughout the range of arthritic diseases. In particular, HAP crystals have been detected in 30-60% of synovial fluid (SF) samples from patients suffering from osteoarthritis (OA) and 33% of those suffering from rheumatoid arthritis (RA). In OA, crystal deposition has been linked to greater joint deterioration. The mechanism of intra-articular calcification is unknown. Nucleation is required to transform a 'metastable' phosphate- and calcium-rich biofluid into one that generates crystals. Ferric ions have been demonstrated to induce crystallization of these stable supersaturated solutions via the process of nucleation. The inflamed arthritic joint is prone to iron loading. Microbleeding from compromised vasculature contributes to intra-articular iron loading in arthritic conditions. Low-molecular-mass redox-active iron complexes have been detected in SF in inflammatory joint diseases. These species are credited with mediating oxidative stress via interaction with peroxides and superoxide. In addition, adventitious low-molecular-mass iron complexes can cause nucleation leading to crystal growth within the joint. Decorporating agents capable of removing this misplaced iron from the arthritic joint would have the joint benefit of relieving oxidative stress and preventing crystal nucleation. Systemic side effects could be overcome by the targeting suitable chelators using bioreductive delivery systems that are activated in hypoxic inflamed synovial tissue.

Arthritis, Rheumatoid↗

PubMed1982

Inflammatory effect of aluminium phosphate on rat paws.

The aim of this experiment was to determine the inflammatory effect of aluminium phosphate on the rat paw and to compare it with those of carrageenan, calcium hydrogen phosphate dihydrate and natural diamond powder. At the probability threshold of the various tests used there was a significant increase in volume of the treated paw relative to the control paw for all the substances at all times, except for the two concentrations of diamond (effect no longer significant from 30 min on), of calcium phosphate (not significant from 2 h), and of aluminium phosphate (not significant from 24 h). The effects were not significantly different between diamond and calcium phosphate (both concentrations). The effects of aluminium phosphate were significantly different from those of the two until at least 2 h after the injection ; there was no significant difference between the two doses of this substance. The kinetics of the effects produced by carrageenan differed from the kinetics of the other materials, its effects were not significantly different from those produced by aluminium phosphate until 2 h and later. The inflammatory effect that we have demonstrated in this study is added information suggesting that in addition to apatite, calcium pyrophosphate dihydrate, and sodium monourate, aluminium compounds can play a role in the unexpected appearance of inflammatory manifestations in haemodialysed patients with chronic renal insufficiency treated with aluminium gels.

Aluminum Compounds↗

PubMed1995

Immunohistochemical study on collagenous proteins and biophysical analysis of crystals in extraskeletal chondroma.

The immunohistological distribution of collagen types I, II, III, and VI in five cases of extraskeletal chondroma was examined and compared with that in six cases of enchondroma. In addition, the composition of crystals deposited in three cases of extraskeletal chondroma were biophysically analyzed with special attention to the relationship between the collagen types of the matrix and the crystal deposition. In extraskeletal chondroma, immunoreactivity of type II collagen in the extracellular matrix and type VI collagen in the pericellular area, which were strongly and diffusely recognized in the normal hyaline cartilage and enchondroma, was diminished. Instead, additional types of collagen, types I and III, were demonstrated in the matrix. Electron roentgenographic microanalysis and infrared light spectroscopic analysis revealed that calcium pyrophosphate dihydrate (CPPD) was included in the crystals of extraskeletal chondroma. CPPD crystals were observed in/around collagen types I and III. The possible relationship between the difference of collagen composition in the matrix and the CPPD crystal deposition is discussed.

Adult↗

PubMed1992

Arthropathies associated with basic calcium phosphate crystals.

Basic calcium phosphate (BCP) crystals refer to a family of crystals including partially carbonate substituted hydroxyapatite, octacalcium phosphate, and tricalcium phosphate. These crystals have been found in and around joints and have been associated with several forms of arthritis and periarthritis. Identification of BCP crystals remains problematic because of the lack of a simple, reliable analytic procedure. Methods currently in use include alizarin red S staining, labelled diphosphonate binding, scanning and transmission electron microscopy with energy dispersive X-ray microanalysis, X-ray diffraction, and atomic force microscopy. Periarthropathies associated with BCP crystals include calcific tendinitis and bursitis. Intra-articular BCP crystal deposition is common in osteoarthritis, often found together with calcium pyrophosphate dihydrate crystals. Uncommon conditions in which BCP crystals are found include destructive shoulder arthropathies, acute inflammatory attacks of arthritis, and erosive arthritis. Secondary deposition of BCP crystals has been observed in chronic renal failure, in patients with "collagen vascular" diseases, following neurologic injury and after local corticosteroid injection.

Arthritis↗

PubMed1999

Clinical trials review: crystal deposition diseases.

This review focuses on several recent clinically-related observations concerning Calcium Pyrophosphate Deposition Disease (CPPDD). Developments include new information on the epidemiology of idiopathic CPPDD in aging, on familial CPPDD, and on associated conditions that predispose to secondary CPPDD. Factors that may precipitate pseudogout, including the use of intra-articular hyaluronan and systemic G-CSF, are also discussed.

Aged↗

PubMed2005

Macroporous calcium phosphate glass-ceramic prepared by two-step pressing technique and using sucrose as a pore former.

Macroporous calcium phosphate glass-ceramic with an initial glass composition of 60CaO.30P2O5.3TiO2.7Na2O in mol% was successfully prepared by sintering the mixture compact consisting of calcium phosphate glass and sucrose powders, which was formed using a two-step pressing technique. After burning off the sucrose phase, a 3D interconnected macroporous structure was formed in the sintered body, in which the skeleton consisting of the calcium phosphate glass-ceramic (including beta-calcium pyrophosphate and beta-tricalcium phosphate as the crystalline phases) was transformed from the initial glass during the sintering. The macropores with several hundred microns in diameter and the large interconnection size (approximately 100 microm), which result from the controllably large-sized sucrose particles and the hot-pressing at a little higher temperature than the sucrose's melting point, are believed to meet the requirements for cell adhesion and bone tissue regeneration well. Moreover, in vitro dissolution behavior study indicates that the calcium phosphate glass-ceramic is soluble to an acetic acid solution of pH 5-7. These, together with the simplicity and feasibility of the innovative fabrication method itself, show that the formed porous glass-ceramic has a promising potential for application to a scaffold for bone tissue engineering.

Biocompatible Materials↗