Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates.

Howell, David S.; Muniz, Ofelia E.; Pita, Julio C.; Enis, Jerry E.

doi:10.1172/jci108228

Cited by 69 publications

(4 citation statements)

References 24 publications

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“…PPi concentrations in urine73 and plasma"" are normal in patients with CPPD crystal deposits, but joint fluid levels are elevated.49 50 7 75 77 However, these elevated levels are not specific for patients with CPPD crystal deposits49 7 77 but have been correlated with the severity of joint degeneration as assessed radiographically.49 50 Howell and his colleagues subsequently showed that hyaline articular cartilage slices from immature, but not adult, rabbits and from osteoarthritic, but not normal, human joints incubated in short-term organ culture liberate PPi into the surrounding medium. 78 We have confirmed these data and also demonstrated PPi liberation from normal adult hyaline cartilage and normal fibrocartilage from several different species.79 The amount of PPi liberated correlated with release of hexosamine into the medium. Cartilage slices that were frozen and thawed failed to release either PPi or hexosamine.…”

Section: Cppd Crystal Clearance From Joint Fluidsupporting

confidence: 65%

Crystals, joints, and consternation.

McCarty¹

1983

Annals of the Rheumatic Diseases

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Section: Cppd Crystal Clearance From Joint Fluidsupporting

confidence: 65%

Crystals, joints, and consternation.

McCarty¹

1983

Annals of the Rheumatic Diseases

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“…The pathomechanism of CPPD crystal deposition remains unknown. Several in vitro studies suggest that the accumulation of inorganic pyrophosphate in the articular cartilage, not synovial tissue, plays an important part in the development of pseudogout [4] , [5] , [6] . Harato and Yoshida [1] and Hirose and Wright [2] reported pseudogout after TKA in the early postoperative period and described its clinical features, including the results of blood tests and physical findings before and after the surgery [1] , [2] .…”

Section: Discussionmentioning

confidence: 99%

Chondrogenesis in the synovial tissue is associated with the onset of pseudogout after total knee arthroplasty

et al. 2016

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Postoperative pseudogout after total knee arthroplasty (TKA) is very rare, and its physical findings are very similar to infectious symptoms. In pseudogout, the mechanism underlying the deposition of calcium pyrophosphate dehydrate crystals remains unclear. Here, we report the histologic findings in a pseudogout attack in the late postoperative period after TKA. She had acute onset of arthritis of the knee 2 years after TKA. Histologic examination showed significant neutrophil infiltration. Interestingly, chondrogenesis was noted in the synovial tissue, and calcium pyrophosphate dehydrate crystals were synthesized mainly at the site of chondrogenesis, suggesting a potential mechanism underlying the occurrence of pseudogout after TKA.

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“…Elevated levels of ePPi are routinely noted in synovial fluids of patients with CPPD deposition disease [2,3]. Chondrocytes are the likely source of the ePPi that participates in the formation of these crystals [4,5]. The elaboration of ePPi by chondrocytes is a bioregulable process, enhanced by transforming growth factor β, ascorbate, retinoic acid, bone morphogenetic protein, transglutaminase, and thyroid hormones and diminished by parathyroid-hormone-related peptide isoforms, insulin-like growth factor-1, tumor necrosis factor α, and interleukin 1.…”

Section: Excess Eppi Promotes Pathologic Mineralization With Cppd Crymentioning

confidence: 99%

The ank gene story

Ryan

2000

Arthritis Res Ther

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Available online http://arthritis-research.com/content/3/2/077 Introduction A landmark investigation into the genetic basis of murine progressive ankylosis has clarified the physiologic role of extracellular inorganic pyrophosphate (ePPi) in suppressing pathologic deposition of basic calcium phosphate (BCP) (an inclusive term for hydroxyapatite, octacalcium phosphate, and tricalcium phosphate) in articular tissue [1]. A cell membrane protein, ANK, affects ePPi concentrations and the balance of mineralization in articular tissues. Excess ePPi promotes pathologic mineralization with CPPD crystalsExcess accumulation of ePPi has long been recognized as an important factor in the mineralization of cartilage with calcium pyrophosphate dihydrate (CPPD) crystals. Elevated levels of ePPi are routinely noted in synovial fluids of patients with CPPD deposition disease [2,3]. Chondrocytes are the likely source of the ePPi that participates in the formation of these crystals [4,5]. The elaboration of ePPi by chondrocytes is a bioregulable process, enhanced by transforming growth factor β, ascorbate, retinoic acid, bone morphogenetic protein, transglutaminase, and thyroid hormones and diminished by parathyroid-hormone-related peptide isoforms, insulin-like growth factor-1, tumor necrosis factor α, and interleukin 1. Porcine chondrocytes from aged donors make more ePPi than do chondrocytes from young donors [6]. Signaling mechanisms involved in the regulation of ePPi formation are poorly understood, but adenylyl cyclase activation decreases and protein kinase C activation increases the accumulation of ePPi in media surrounding cartilage or chondrocyte cultures [7]. In addition to causing CPPD crystal formation, excess ePPi accumulation may also affect BCP mineralization.CPPD crystal deposits and elevated ePPi levels are particularly prominent in adult hypophosphatasia, congenital deficiency of tissue-nonspecific alkaline phosphatase. In hypophosphatasia, the predominant phenotypic disease expressions are rickets and osteomalacia. Murine models of hypophosphatasia indicate that the nucleation and initial growth of BCP crystals within matrix vesicles of mineralizing CommentaryThe ank gene story AbstractThe underlying molecular defect resulting in the abnormal calcification observed in ank/ank mice has been identified. The responsible nonsense mutation affects the protein product of ank, resulting in diminished production of extracellular inorganic pyrophosphate, an important inhibitor of nucleation and of the growth of apatite crystals. The ank gene product is one of several cell membrane proteins, including ectonucleoside triphosphate pyrophosphohydrolase enzymes and alkaline phosphatase, that regulate extracellular inorganic pyrophosphate levels and thereby regulate mineralization.

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Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates.

Cited by 69 publications

References 24 publications

Crystals, joints, and consternation.

Crystals, joints, and consternation.

Chondrogenesis in the synovial tissue is associated with the onset of pseudogout after total knee arthroplasty

The ank gene story

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