Abstract
The biological effects and cellular activations triggered by monosodium urate (MSU) and calcium pyrophosphate dihydrate (monoclinic: m-CPPD) crystals might be modulated by protein coating on the crystal surface. This study is aimed at: (i) Identifying proteins adsorbed on m-CPPD crystals, and the underlying mechanisms of protein adsorption, and (ii) to understand how protein coating did modulate the inflammatory properties of m-CPPD crystals. The effects of protein coating were assessed in vitro using primary macrophages and THP1 monocytes. Physico-chemical studies on the adsorption of bovine serum albumin (BSA) upon m-CPPD crystals were performed. Adsorption of serum proteins, and BSA on MSU, as well as upon m-CPPD crystals, inhibited their capacity to induce interleukin-1-β secretions, along with a decreased ATP secretion, and a disturbance of mitochondrial membrane depolarization, suggesting an alteration of NLRP3 inflammasome activation. Proteomic analysis identified numerous m-CPPD-associated proteins including hemoglobin, complement, albumin, apolipoproteins and coagulation factors. BSA adsorption on m-CPPD crystals followed a Langmuir-Freundlich isotherm, suggesting that it could modulate m-CPPD crystal-induced cell responses through crystal/cell-membrane interaction. BSA is adsorbed on m-CPPD crystals with weak interactions, confirmed by the preliminary AFM study, but strong interactions of BSA molecules with each other occurred favoring crystal agglomeration, which might contribute to a decrease in the inflammatory properties of m-CPPD crystals. These findings give new insights into the pathogenesis of crystal-related rheumatic diseases and subsequently may open the way for new therapeutic approaches.
Highlights
Calcium orthophosphates such as carbonated-apatites, calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) are three main types of crystals associated with rheumatic diseases, responsible for hydroxyapatite rheumatism, CPP deposition disease and gout, respectively.Prevalence of these crystal depositions is high, occurring for example in more than 17.5% of people over 75 years for CPPD crystals, and between 0.9 and more than 10% for MSU crystals [1,2,3]
We first assessed the effect of MSU and m-CPPD crystals which were pre-incubated with fetal bovine serum (FBS) on IL-1β secretion by the human cell line THP1
Our results suggested that protein coating decreased MSU and m-CPPD crystal-induced IL-1β production through NLRP3 inflammasome inhibition
Summary
Calcium orthophosphates such as carbonated-apatites, calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) are three main types of crystals associated with rheumatic diseases, responsible for hydroxyapatite rheumatism, CPP deposition disease and gout, respectively.Prevalence of these crystal depositions is high, occurring for example in more than 17.5% of people over 75 years for CPPD crystals, and between 0.9 and more than 10% for MSU crystals [1,2,3]. Monoclinic and triclinic CPPD phases (m-CPPD and t-CPPD respectively) are the two CPPD crystals identified in human tissues, while the existence of precursor forms such as monoclinic calcium pyrophosphate tetrahydrate beta (m-CPPTβ), and amorphous calcium pyrophosphate (a-CPP) phases have been suggested by in vitro studies [4,5,6]. These crystals remain mostly asymptomatic, they can induce recurrent, self-resolving and interleukin (IL)-1β-driven inflammation reactions [7,8,9]. We speculated that modification of protein coating on the crystal surface might modulate immune cell responses and contribute to these different clinical phenotypes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
