pyrophosphate and Cartilage-Diseases

We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease.. Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.

Topics: Abnormalities, Multiple; Aortic Diseases; Basal Ganglia Diseases; Calcinosis; Cartilage Diseases; Dental Enamel Hypoplasia; Diphosphates; Enzyme Replacement Therapy; Gaucher Disease; Hand Deformities, Congenital; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia; Interferons; Metacarpus; Muscular Diseases; Odontodysplasia; Osteoporosis; Phosphates; Progeria; Pseudoxanthoma Elasticum; Pulmonary Valve Stenosis; Vascular Calcification

The preliminary results obtained in a study of the use of scintigraphy with Tc 99 PYP for the evaluation of meniscal lesions of the knee are presented. Three different captation curves are described. Those with an elevated peak and a restricted base are characteristic of meniscal lesions. The use of this method in a series of 50 patients in whom meniscal lesions were suspected demonstrated a high diagnostic sensitivity and specificity with regard to the presence of the lesion, but not to its type.

Topics: Adolescent; Adult; Cartilage Diseases; Diphosphates; Female; Humans; Male; Menisci, Tibial; Middle Aged; Predictive Value of Tests; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Aged; Arthritis, Infectious; Calcium Pyrophosphate; Cartilage Diseases; Diphosphates; Gout; Humans; Male

Topics: Animals; Calcium Pyrophosphate; Cartilage Diseases; Diphosphates; Disease Models, Animal; Humans; Macaca mulatta; Microscopy, Electron, Scanning; Monkey Diseases

Naturally occurring deposition of calcium pyrophosphate has been identified in six rhesus monkeys following acute episodes of trauma and various septicemias. Scanning electron microscopy with energy-dispersive X-ray analytical system and single crystal electron diffraction studies were used to identify the crystals within the articular cartilage. The osteoarthritis grading system was used to determine the degree of cartilage degenerative changes.

Topics: Animals; Calcium Pyrophosphate; Cartilage Diseases; Cartilage, Articular; Diphosphates; Female; Knee Joint; Macaca mulatta; Male; Microscopy, Electron, Scanning; Monkey Diseases; Osteoarthritis; Synovitis; X-Ray Diffraction

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 II. 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 5'nucleotidase 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.

Topics: Adenosine Triphosphate; Aged; Alkaline Phosphatase; Calcium Pyrophosphate; Cartilage Diseases; Cartilage, Articular; Cations, Divalent; Chromatography; Diphosphates; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Middle Aged; Nucleotidases; Osteoarthritis; Phosphoric Monoester Hydrolases; Pyrophosphatases

Topics: Adult; Biopsy; Bone Matrix; Calcium Phosphates; Cartilage Diseases; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Femur; Histocytochemistry; Humans; Microradiography; Microscopy, Electron; Microscopy, Polarization; Middle Aged; X-Ray Diffraction

Topics: Arthritis; Calculi; Cartilage Diseases; Colchicine; Crystallization; Diphosphates; Female; Humans; Joint Diseases; Kidney Failure, Chronic; Knee; Male; Periarthritis; Radiography; Shoulder; Synovial Fluid; Synovitis; Wrist

Topics: Acromegaly; Adult; Calcinosis; Calcium Phosphates; Cartilage Diseases; Diagnosis, Differential; Diphosphates; Gout; Hemochromatosis; Humans; Hyperparathyroidism; Joints; Male; Microscopy, Polarization; Middle Aged; Radiography; Terminology as Topic