MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize other research findings regarding the use of miRNA from these two sources as biomarkers in diagnostics and clinical use. The challenges in using miRNA from these two sources in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics.

Chronic periodontitis (CP) is an oral cavity disease arising from chronic inflammation of the periodontal tissues. Exosomes are lipid vesicles that are enriched in specific microRNAs (miRNAs), potentially providing a disease-specific diagnostic signature. To assess the value of exosomal miRNAs as biomarkers for CP, 8 plasma- and 8 salivary-exosomal miRNAs samples were profiled using Agilent platform (comparative study). From 2,549 probed miRNAs, 33 miRNAs were significantly down-regulated in CP as compared to healthy plasma samples. Whereas, 1,995 miRNAs (1,985 down-regulated and 10 up-regulated) were differentially expressed in the CP as compared to healthy saliva samples. hsa-miR-let-7d [FC = −26.76; AUC = 1; r = −0.728 [p-value = 0.04]), hsa-miR-126-3p (FC = −24.02; AUC = 1; r = −0.723 [p-value = 0.043]) and hsa-miR-199a-3p (FC = −22.94; AUC = 1; r = −0.731 [p-value = 0.039]) are worth to be furthered studied for plasma-exosomal samples. Meanwhile, for salivary-exosomal samples, hsa-miR-125a-3p (FC = 2.03; AUC = 1; r = 0.91 [p-value = 0.02]) is worth to be furthered studied. These miRNAs are the reliable candidates for the development of periodontitis biomarker, as they were significantly expressed differently between CP and healthy samples, have a good discriminatory value and strongly correlate with the mean of PPD. These findings highlight the potential of exosomal miRNAs profiling in the diagnosis from both sourced as well as provide new insights into the molecular mechanisms involved in CP.

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.