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Cell Mol Life Sci. 2017 Oct;74(19):3599-3611. doi: 10.1007/s00018-017-2535-8. Epub 2017 May 10.

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

Author information

1
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089, Budapest, Hungary.
2
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
3
Department of Physiology, Semmelweis University, Budapest, Hungary.
4
MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, Budapest, Hungary.
5
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
6
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089, Budapest, Hungary. gyorgyngy@gmail.com.
7
Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. gyorgyngy@gmail.com.

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.

KEYWORDS:

Exosome; Microvesicle; Osteoclast; Psoriatic arthritis; Rheumatoid arthritis

PMID:
28493076
DOI:
10.1007/s00018-017-2535-8
[Indexed for MEDLINE]

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