Molecular signatures of extracellular vesicles in oral fluids of periodontitis patients

Chaparro, Alejandra; Aracena, Laura Weber; Fuentes, Ornella Realini; Albers, Daniela; Ríos, M Hernández; Lobos, Valeria Ramírez; Rocca, Andrés Pascual-La; Molina, José Nart; Varas, Víctor Beltrán; Acuña-Gallardo, Stephanie; Ruiz, Antonio Sanz

doi:10.1111/odi.13338

Cited by 34 publications

(40 citation statements)

References 31 publications

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“…The alteration of body fluid EV concentrations in pathological states has been described in both infectious and inflammatory models [ 35 , 36 ]. In patients with periodontitis, there is a higher concentration of EVs in gingival crevicular fluid, which correlates with the clinical inflammatory periodontal parameters [ 37 ]. A similar phenomenon is observed in patients with human African trypanosomiasis, where late stage patients have a higher concentration of EVs in cerebrospinal fluid when compared to early and intermediate stages, with these EVs also showing different functional properties such as altering astrocyte protein expression in vitro [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

Madeira

Romera

Buck

et al. 2021

Journal of Immunology Research

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Chagas disease, a neglected tropical disease (NTD) caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), is a major public health problem. It was initially restricted to Latin America, but it is now expanding globally. Host and pathogen interactions are crucial in the establishment of disease, and since 1970, it has been known that eukaryotic cells release extracellular vesicles (EVs), which in turn have an important role in intercellular communication in physiological and pathological conditions. Our study proposed to characterize and compare circulating EVs isolated from the plasma of chronic Chagas disease (CCD) patients and controls. For this, peripheral blood was collected from patients and controls, and mononuclear cells (PBMCs) were isolated and stimulated with parasite EVs, showing that patient cells released fewer EVs than control cells. Then, after plasma separation followed by EV total shedding enrichment, the samples were subjected to ultracentrifugation to isolate the circulating EVs, which then had their size and concentration characterized by nanoparticle tracking analysis (NTA). This showed that patients had a lower concentration of circulating EVs while there were no differences in size, corroborating the in vitro data. Additionally, circulating EVs were incubated with THP-1 cells (macrophages) that, after the interaction, had their supernatant analyzed by ELISA for cytokine detection. In relation to their ability to induce cytokine production, the CCD patient EVs were able to induce a differential production of IFN-γ and IL-17 in relation to controls, with differences being more evident in earlier/less severe stages of the disease. In summary, a decreased concentration of circulating EVs associated with differential activation of the immunological system in patients with CCD is related to parasite persistence and the establishment of chronic disease. It is also a potential biomarker for monitoring disease progression.

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Section: Discussionmentioning

confidence: 99%

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

Madeira

Romera

Buck

et al. 2021

Journal of Immunology Research

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“…In an additional exploratory study, Chaparro et al detected the total concentration of EVs in gingival crevicular fluid (GCF) and saliva samples from patients with healthy gums/gingivitis or periodontitis. The authors did not detect significant differences in salivary EVs but found significant increases in the total concentration of medium/large EVs in GCF 22 . Since GCF consists of serum and locally generated components, including tissue breakdown products, inflammatory mediators, and antibodies in response to oral microorganisms, we speculate that there could be significant differences in GCF exosome levels between periodontitis patients and healthy individuals.…”

Section: Exosomes As Diagnostic Biomarkersmentioning

confidence: 78%

Emerging role of exosomes in craniofacial and dental applications

Xing¹,

Han²,

Li³

et al. 2020

Theranostics

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Exosomes, a specific subgroup of extracellular vesicles that are secreted by cells, have been recognized as important mediators of intercellular communication. They participate in a diverse range of physiological and pathological processes. Given the capability of exosomes to carry molecular cargos and transfer bioactive components, exosome-based disease diagnosis and therapeutics have been extensively studied over the past few decades. Herein, we highlight the emerging applications of exosomes as biomarkers and therapeutic agents in the craniofacial and dental field. Moreover, we discuss the current challenges and future perspectives of exosomes in clinical applications.

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“…Periodontal ligament -derived stem cells were used to treat PD in humans (clinical trial identifier: NCT02523651). Apart from oral stem cells, other regenerative approaches such as the use of biomaterials, by themselves or used as scaffolds to load cells or drugs, extracellular vesicles, hold promising therapeutic future to repair and grow bone [69,70]. Nevertheless, additional studies are needed to determine the beneficial effects of using dental-derived stem cells and LLP2A-Ale for PDinduced bone loss.…”

Section: Discussionmentioning

confidence: 99%

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

Jiang

Liu

et al. 2020

BMC Pharmacol Toxicol

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Background Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Methods PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/− MSCs. LLP2A-Ale +/− MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.

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Molecular signatures of extracellular vesicles in oral fluids of periodontitis patients

Cited by 34 publications

References 31 publications

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

Emerging role of exosomes in craniofacial and dental applications

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

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