european crystal network workshop

    Influence of magnesium, iron or zinc ions on calcium pyrophosphate dihydrates crystallization involved in osteoarthritis.


    Ley-Ngardigal Kemie1-2, Combes Christèle2, Teychene Sébastien1, Rey Christian2, Sarda Stéphanie3, Gras Pierre2, Biscans Béatrice1.

    1Université de Toulouse, Laboratoire de Génie Chimique UMR5503 CNRS-INPT-UPS, ENSIACET, 4 allée E. Monso, CS 84234, 31432 Toulouse Cedex 4. 2Université de Toulouse, CIRIMAT UMR5085 INPT-CNRS-UPS, ENSIACET, 4 allée E. Monso, CS 44362, 31030 Toulouse Cedex 4. 3Université de Toulouse, CIRIMAT, UMR 5085 INPT-CNRS-UPS, Université Paul Sabatier, 31062Toulouse.


    Abstract: Osteoarthritis (OA) affects about ten million people in France. The presence of microcrystals including those of calcium pyrophosphate (CPP) dihydrates (Ca2P2O7•2H2O; monoand/ or triclinic: m-CPPD and/or t-CPPD respectively) in the joints has been identified as an aggravating factor of OA. However the conditions of formation of both CPPD phases and their order of appearance remain unknown. Understanding the mechanisms of crystallization of CPP phases in the presence or absence of additives is a key step in the medium to long term development of a therapeutic treatment. Cheng et al. (1981) have shown that Mg2+ promotes production of m-CPPD phase rather than t-CPPD in a study where the Mg2+ and Ca2+ concentrations varied simultaneously during the CPP synthesis which conditions were moreover not controlled to precipitate a specific phase of CPP. The aim of this study is to synthesize in vitro by precipitation hydrated CPP phases of b iological interest and to analyze the effect of ionic additives on the precipitation of t-CPPD phase under controlled conditions. Three types of ions of biological interest have been tested: Mg2+, Zn2+ and Fe3+. To achieve the objective, the synthesis method developed by Gras et al. (2013), a precipitation by simultaneous addition of two reagent solutions of calcium nitrate and potassium pyrophosphate in an ammonium acetate buffer solution, was transposed in stirred reactor. Powders synthesized were analyzed by X-ray diffraction and scanning electron microscopy. At pH 3.6, 90°C and in the absence of any ionic additives, we mainly obtained t-CPPD phase. We showed that in the same conditions but in the presence of each of the ionic additive selected, we obtained a mixture of m- CPPD, t-CPPD, and a few amount of amorphous CPP phases. We also demonstrated that the presence of 1 mM of zinc or magnesium ions during the precipitation, leads to an increase of the m- CPPD/t-CPPD mass ratio in the resulting product. These results may help to explain why m-CPPD phase is identified in vivo in the joint of arthritic patients while this pure phase is very difficult to obtain in vitro (very narrow temperature-pH domain in a medium free of any ionic additives). These results could also provide indications on the order of appearance and potential evolution of m-CPPD and t- CPPD phases formed in vivo in osteoarthritic joints. Cheng et al. J. Rheumatol.1981, 8: 772-782. Gras et al. Eur. J. Inorg. Chem. 2013,.34: 5886-5895.