Crystal structure of monoclinic calcium pyrophosphate dihydrate (m-CPPD) involved in inflammatory reactions and osteoarthritis

Gras, Pierre; Rey, Christian; André, G.; Charvillat, Cédric; Sarda, Stéphanie; Combes, Christèle

doi:10.1107/s2052520615021563

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…The organization of atoms and molecules on the surface of the different CPP crystals, and a fortiori on the a-CPP phase, presents a wide variety of configurations. The pyrophosphate molecule orientation and the number of calcium vary considerably between the fully hydrated basal surface of m-CPPTβ with no pyrophosphate molecules on the surface and the m-CPPD crystal faces with pyrophosphate molecules exposed almost parallel to this surface ( 53 ). Hence, the m-CPPD crystals could present enhanced properties of interaction with the environment, which could be responsible for its higher inflammatory property.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

et al. 2018

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Background: Calcium pyrophosphate (CPP) microcrystal deposition is associated with wide clinical phenotypes, including acute and chronic arthritis, that are interleukin 1β (IL-1β)-driven. Two CPP microcrystals, namely monoclinic and triclinic CPP dihydrates (m- and t-CPPD), have been identified in human tissues in different proportions according to clinical features. m-CPP tetrahydrate beta (m-CPPTβ) and amorphous CPP (a-CPP) phases are considered as m- and t-CPPD crystal precursors in vitro.Objectives: We aimed to decipher the inflammatory properties of the three crystalline phases and one amorphous CPP phase and the intracellular pathways involved.Methods: The four synthesized CPP phases and monosodium urate crystals (MSU, as a control) were used in vitro to stimulate the human monocytic leukemia THP-1 cell line or bone marrow-derived macrophages (BMDM) isolated from WT or NLRP3 KO mice. The gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR; IL-1β, IL-6 and IL-8 production by ELISA; and mitogen-activated protein kinase (MAPK) activation by immunoblot analysis. NF-κB activation was determined in THP-1 cells containing a reporter plasmid. In vivo, the inflammatory potential of CPP phases was assessed with the murine air pouch model via cell analysis and production of IL-1β and CXCL1 in the exudate. The role of NF-κB was determined by a pharmacological approach, both in vivo and in vitro.Results: In vitro, IL-1β production induced by m- and t-CPPD and m-CPPTβ crystals was NLRP3 inflammasome dependent. m-CPPD crystals were the most inflammatory by inducing a faster and higher production and gene expression of IL-1β, IL-6, and IL-8 than t-CPPD, m-CPPTβ and MSU crystals. The a-CPP phase did not show an inflammatory property. Accordingly, m-CPPD crystals led to stronger activation of NF-κB, p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) MAPKs. Inhibition of NF-κB completely abrogated IL-1β and IL-8 synthesis and secretion induced by all CPP crystals. Also, inhibition of JNK and ERK1/2 MAPKs decreased both IL-1β secretion and NF-κB activation induced by CPP crystals. In vivo, IL-1β and CXCL1 production and neutrophil infiltration induced by m-CPPD crystals were greatly decreased by NF-κB inhibitor treatment.Conclusion: Our results suggest that the inflammatory potential of different CPP crystals relies on their ability to activate the MAPK-dependent NF-κB pathway. Studies are ongoing to investigate the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

et al. 2018

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“…The m‐CPPD can be more surface‐active compared to the t‐CPPD form, and it can be expected that the m‐CPPD forms have a higher inflammatory potential than the t‐CPPD forms . This situation can be attributed to the fact that the m‐CPPD forms have a higher surface area‐to‐volume ratio .…”

Section: Introductionmentioning

confidence: 99%

Multidimensional Population Balance Modeling for Pathological Calcium Pyrophosphate Dihydrate Crystals in the Presence of Amino Acids

2020

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A multidimensional population balance model was applied to elaborate the effects of amino acids on the crystallization mechanisms of calcium pyrophosphate dihydrate crystals. Breakage and growth terms defined in the model were expressed in two dimensions depending on the sizes. The exponential hyperbolic function based on the particle sizes was selected for expressing the growth. The model was resolved by using the finite differences method. It was detected that in the nonadditive media, the growth along the length-1 is extremely dominant against both the growth along the length-2 and the breakage. However, it was discovered that the amino acids made the crystals more fragile, and the breakage at certain size ranges and certain concentrations of amino acids was the dominant mechanism. In any case, it was proven that both growth and breakage are suppressed considerably in the amino acid-containing media.

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“…According to the experimental results provided by Gras et al [28], the structure of Cu2P2O7*2H2O (m-CuPPD) crystallized in a P21/n space group includes pyrophosphate ions and two water molecules (Figure 1). Each formula unit is repeated four times per cell.…”

Section: Resultsmentioning

confidence: 96%

Structure and Properties of Copper Pyrophosphate by First-Principle Calculations

et al. 2022

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Investigated the structural, electronic, and magnetic properties of copper pyrophosphate dihydrate (CuPPD) by the first-principle calculations based on the density functional theory (DFT). Simulations were performed with the generalized gradient approximation (GGA) of the exchange-correlation functional (Exc) supplemented by an on-site Coulomb self-interaction (U–Hubbard term). It was confirmed that the GGA method did not provide a satisfactory result in predicting the electronic energy band gap width (Eg) of the CuPPD crystals. Simultaneously, we measured the Eg of CuPPD nanocrystal placed inside mesoporous silica using the ultraviolet–visible spectroscopy (UV–VIS) technique. The proposed Hubbard correction for Cu-3d and O-2p states at U = 4.64 eV reproduces the experimental value of Eg = 2.34 eV. The electronic properties presented in this study and the results of UV–VIS investigations likely identify the semiconductor character of CuPPD crystal, which raises the prospect of using it as a component determining functional properties of nanomaterials, including quantum dots.

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Crystal structure of monoclinic calcium pyrophosphate dihydrate (m-CPPD) involved in inflammatory reactions and osteoarthritis

Cited by 19 publications

References 34 publications

Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

Multidimensional Population Balance Modeling for Pathological Calcium Pyrophosphate Dihydrate Crystals in the Presence of Amino Acids

Structure and Properties of Copper Pyrophosphate by First-Principle Calculations

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