Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies

Marton, N. et al. (2017) Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies. Cellular and Molecular Life Sciences, 74(19), pp. 3599-3611. (doi:10.1007/s00018-017-2535-8) (PMID:28493076)

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Abstract

Objective: Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis. Methods: Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14+ monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted. Results: EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14+ cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect. Conclusions: Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.

Item Type:Articles
Additional Information:This work was supported by the Hungarian Scientific Research Fund OTKA-NN111023, OTKA-NKFIH #11958; MEDINPROT and BMBS COST Action BM1202 ME HAD. Funding was provided by National Heart Program (Grant Nos. OTKA 120237, NKFIA, and KP-16-1-2016-0017).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Goodyear, Professor Carl and Meier, Dr Florian
Authors: Marton, N., Kovács, O. T., Baricza, E., Kittel, Á., Győri, D., Mócsai, A., Meier, F. M.P., Goodyear, C. S., McInnes, I. B., Buzás, E. I., and Nagy, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cellular and Molecular Life Sciences
Publisher:Springer
ISSN:1420-682X
ISSN (Online):1420-9071
Published Online:10 May 2017

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