Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction

Abstract

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Microparticles as autoantigens in systemic lupus erythematosus

“…Some studies have documented differences in the proteins present in MPs generated in vitro under different conditions; it is not yet clear whether differences in proteins reflect a change in the proteome of the cell prior to particle release or a difference in the mechanisms of particle formation and the incorporation of different cell compartments. Importantly, cytokines can be present on vesicles as well as apoptotic bodies …”

“…Importantly, cytokines can be present on vesicles as well as apoptotic bodies. 43,44 In studies on blood MPs, Ostergaard and colleagues provided evidence that MPs found in lupus differ from those in healthy controls or patients with systemic sclerosis. 45 These studies demonstrated distinctive features such as a reduction in platelet and mitochondrial proteins, derangement in cytoskeletal proteins and increase in proteins involved in glycolytic enzymes and apoptosis.…”

Increased circulating microparticles in streptozotocin‐induced diabetes propagate inflammation contributing to microvascular dysfunction

“…; Pasquier et al . ). MPs, the small plasma membrane‐derived vesicles released during cell activation and apoptosis, often retain membrane surface molecules, cytoplasmic proteins, lipids and nucleic acids from their parent cells, and have been recognized as important biomarkers of disease status.…”

“…Increasing clinical evidence indicates that circulating microparticles (MPs) are markedly elevated in patients with inflammation-linked cardiovascular diseases, including diabetes (Agouni et al 2008;Leroyer et al 2008a;Jung et al 2009;Boilard et al 2010;Helal et al 2010;Meziani et al 2010;Tramontano et al 2010;Mastronardi et al 2011;Pasquier et al 2017). MPs, the small plasma membrane-derived vesicles released during cell activation and apoptosis, often retain membrane surface molecules, cytoplasmic proteins, lipids and nucleic acids from their parent cells, and have been recognized as important biomarkers of disease status.…”

“…MPs, the small plasma membrane-derived vesicles released during cell activation and apoptosis, often retain membrane surface molecules, cytoplasmic proteins, lipids and nucleic acids from their parent cells, and have been recognized as important biomarkers of disease status. While increasing numbers of studies have focused on the potential roles of circulating MPs as diagnostic tools La Marca & Fierabracci, 2017;Michalska-Jakubus et al 2017;Pasquier et al 2017;Ridger et al 2017;Hosseinzadeh et al 2018), their precise impact on the pathogenesis and progression of diseases remains obscure (Nomura et al 2008). Currently, functional MP studies have been conducted mainly on specific cell type-derived MPs using in vitro approaches (Leroyer et al 2008;Badimon et al 2017;Burger et al 2017).…”