A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis

1977 ◽  
Vol 7 (1) ◽  
pp. 153-155 ◽  
Author(s):  
Isaias Spilberg ◽  
Alberto Gallacher ◽  
Brian Mandell ◽  
David Rosenberg
Keyword(s):  
Mechanism Of Action ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Cppd Crystal ◽  
Pyrophosphate Dihydrate ◽  
Anti Inflammatory ◽  
Crystal Induced Arthritis

scholarly journals Calcium Pyrophosphate Dihydrate Crystals Increase the Granulocyte/Monocyte Progenitor (GMP) and Enhance Granulocyte and Monocyte Differentiation In Vivo

2020 ◽  
Vol 22 (1) ◽  
pp. 262
Author(s):  
Nobuyuki Onai ◽  
Chie Ogasawara
Keyword(s):  
Cell Differentiation ◽  
Peripheral Blood ◽  
Calcium Pyrophosphate ◽  
Hematopoietic Progenitor Cell ◽  
Calcium Pyrophosphate Dihydrate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Hematopoietic Stem ◽  
Cppd Crystal ◽  
Pyrophosphate Dihydrate

Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a “danger signal” to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout.

scholarly journals Upregulation of ANK Protein Expression in Joint Tissue in Calcium Pyrophosphate Dihydrate Crystal Deposition Disease

2013 ◽  
Vol 41 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Miwa Uzuki ◽  
Takashi Sawai ◽  
Lawrence M. Ryan ◽  
Ann K. Rosenthal ◽  
Ikuko Masuda
Keyword(s):  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Crystal Formation ◽  
Type X Collagen ◽  
Crystal Deposition ◽  
Chondrocyte Hypertrophy ◽  
Inorganic Pyrophosphate ◽  
Crystal Deposition Disease ◽  
Cppd Crystal ◽  
Pyrophosphate Dihydrate

Objective.Accumulation of excess extracellular inorganic pyrophosphate leads to calcium pyrophosphate dihydrate (CPPD) crystal formation in articular cartilage. CPPD crystal formation occurs near morphologically abnormal chondrocytes resembling hypertrophic chondrocytes. The ANK protein was recently implicated as an important factor in the transport of intracellular inorganic pyrophosphate across the cell membrane. We characterized ANK in joint tissues from patients with and without CPPD deposition and correlated the presence of ANK with markers of chondrocyte hypertrophy.Methods.Articular tissues were obtained from 24 patients with CPPD crystal deposition disease, 11 patients with osteoarthritis (OA) without crystals, and 6 controls. We determined the number of ANK–positive cells in joint tissues using immunohistochemistry and in situ hybridization, and correlated ANK positivity with markers of chondrocyte hypertrophy including Runx2, type X collagen, osteopontin (OPN), and osteocalcin (OCN).Results.ANK was detected in synoviocytes, chondrocytes, osteoblasts, and osteocytes. ANK was seen extracellularly only in the matrix of cartilage and meniscus. The number of ANK-positive cells was significantly higher in CPPD than in OA or normal joint tissues. The amount and intensity of ANK immunoreactivity reached maximum levels in the large chondrocytes around crystal deposits. ANK was similarly distributed to and significantly correlated with Runx2, type X collagen, OPN, and OCN.Conclusion.ANK levels were higher in articular tissues from patients with CPPD deposition. ANK was concentrated around crystal deposits and correlated with markers of chondrocyte hypertrophy. These findings support a role for ANK in CPPD crystal formation in cartilage.

X-Ray Characteristics of Wrists in Calcium Pyrophosphate Crystal Deposition Disease

1997 ◽  
Vol 22 (5) ◽  
pp. 659-661 ◽  
Author(s):  
Y. TANIGUCHI ◽  
M. YOSHIDA ◽  
T. TAMAKI
Keyword(s):  
Japanese Patients ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Crystal Deposition ◽  
X Ray ◽  
Crystal Deposition Disease ◽  
Cppd Crystal ◽  
Deposition Disease ◽  
Pyrophosphate Dihydrate ◽  
Slac Wrist

Deposition of calcium pyrophosphate dihydrate (CPPD) crystals has been considered to be a cause of scapholunate advanced collapse (SLAC) wrist. The aim of this study was to look at X-ray changes in wrist joints affected by CPPD crystal deposition disease and to determine whether crystal deposition is a cause of SLAC wrist. A total of 150 wrists of 78 patients with CPPD crystal deposition disease were examined. In our population of Japanese patients with CPPD crystal deposition disease, the incidence of SLAC wrist was very low, and no case of Stage III SLAC wrist was found. We therefore conclude that SLAC wrist is not a radiographic characteristic of CPPD crystal deposition disease and that pyrophosphate crystal deposition cannot be a major cause of SLAC wrist.

Mercaptopyruvate Inhibits Tissue-Nonspecific Alkaline Phosphatase and Calcium Pyrophosphate Dihydrate Crystal Dissolution

2009 ◽  
Vol 36 (12) ◽  
pp. 2758-2765 ◽  
Author(s):  
JOVIL V.A. KANNAMPUZHA ◽  
JINDRA H. TUPY ◽  
KENNETH P.H. PRITZKER
Keyword(s):  
Amino Acids ◽  
Alkaline Phosphatase ◽  
Enzyme Inhibition ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Crystal Dissolution ◽  
Cppd Crystal ◽  
Endogenous Amino Acids ◽  
Pyrophosphate Dihydrate ◽  
Tissue Nonspecific Alkaline Phosphatase

Objective.The enzymatic activities of tissue-nonspecific alkaline phosphatase (TNAP) including capacity to inhibit calcium pyrophosphate dihydrate (CPPD) crystal dissolution are known to be inhibited by endogenous amino acids, notably cysteine. As cysteine is recognized as a strong TNAP inhibitor, we investigated whether cysteine-related metabolites such as mercaptopyruvate (MPA) could show similar enzyme inhibition effects and, if so, whether these effects might be synergistic with cysteine at approximate physiologic concentrations of the amino acids.Methods.We studied the inhibitory effects of MPA as well as MPA and cysteine combined in equimolar concentrations on TNAP’s phosphatase, inorganic pyrophosphatase, and CPPD crystal dissolution activities. Kinetic parameters Vmax, KM, concentration for 50% inhibition (I50), inhibitor constant (KI), and specific activities calculated from initial velocity, Eadie-Hofstee, Simple, Dixon, and secondary plots were used to assess enzyme inhibition.Results.MPA significantly inhibited TNAP’s phosphatase and pyrophosphatase activities at 10× and 100× physiological concentrations. In the presence of calcium [Ca2+] and [Mg2+] = 1 mM, MPA inhibited uncompetitively TNAP’s phosphatase activity and inhibited noncompetitively its pyrophosphatase activity. CPPD crystal dissolution activity was also inhibited. Cysteine and MPA together in equimolar concentrations inhibited TNAP enzyme activities and CPPD crystal dissolution much more effectively than MPA or cysteine alone, reducing CPPD dissolution to 38% of controls at approximate physiologic inhibitor concentrations.Conclusion.Endogenous amino acids like cysteine and its derivative MPA have the capacity to inhibit TNAP activities at physiologic concentrations. Downregulation of their inhibiting concentration in the cartilage interstitial fluid environment may provide a therapeutic avenue to controlled dissolution of CPPD crystal deposition in tissues.

scholarly journals Dexamethasone Promotes Calcium Pyrophosphate Dihydrate Crystal Formation by Articular Chondrocytes

2009 ◽  
Vol 36 (1) ◽  
pp. 163-169 ◽  
Author(s):  
MARK FAHEY ◽  
ELIZABETH MITTON ◽  
EMILY MUTH ◽  
ANN K. ROSENTHAL
Keyword(s):  
Alkaline Phosphatase ◽  
Articular Chondrocytes ◽  
Calcium Pyrophosphate ◽  
Factor Xiiia ◽  
Nucleoside Triphosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Crystal Formation ◽  
Cppd Crystal ◽  
Tissue Culture Model ◽  
Pyrophosphate Dihydrate

Objective.Calcium pyrophosphate dihydrate (CPPD) crystals are commonly found in osteoarthritic joints and correlate with a poor prognosis. Intraarticular corticosteroids, such as dexamethasone (Dxm), are commonly used therapies for osteoarthritis with or without CPPD deposition. Dxm has variable effects in mineralization models. We investigated the effects of Dxm on CPPD crystal formation in a well established tissue culture model.Methods.Porcine articular chondrocytes were incubated with ATP to generate CPPD crystals. Chondrocytes incubated with or without ATP were exposed to 1–100 nM Dxm in the presence of 45Ca. Mineralization was measured by 45Ca uptake in the cell layer. We also investigated the effect of Dxm on mineralization-regulating enzymes such as alkaline phosphatase, nucleoside triphosphate pyrophosphohydrolase (NTPPPH), and transglutaminase.Results.Dxm significantly increased ATP-induced mineralization by articular chondrocytes. While alkaline phosphatase and NTPPPH activities were unchanged by Dxm, transglutaminase activity increased in a dose-responsive manner. Levels of Factor XIIIA mRNA and protein were increased by Dxm, while type II Tgase protein was unchanged. Transglutaminase inhibitors suppressed Dxminduced increases in CPPD crystal formation.Conclusion.These findings suggest a potential for Dxm to contribute to pathologic mineralization in cartilage and reinforce a central role for the transglutaminase enzymes in CPPD crystal formation.

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