MicroRNAs and Immunity in Periodontal Health and Disease
Recently I decided to start a virtual journal club for dental hygienists, it has been a lot of fun. I chose the review article I plan to highlight in this post as an article to highlight in one of the journal club meetings, however upon reading it, it became apparent that I could not do this review justice in a one-hour journal club meeting.  That revelation is what prompted this blog post. This article is heavy in science and specifically immunology. Full disclosure, I am not an expert in the area of immunology, but I have a little background on the subject which gives me confidence that I can deliver a summary of the findings in this review in a manner that is factual and relevant to the area of dental hygiene. So, buckle up as we dive into this review.
A quick review of MicroRNAs
Considering microRNAs (miRNAs) were first discovered in 1993, I must assume some readers are not familiar with it at all, therefore I want to start with a brief explanation of what miRNAs are and what it does…. or at least what we know it does to date.
miRNAs are a class of non-coding RNAs that play an important role in gene expression. miRNAs are powerful gene regulators, but also control mRNA stability, translation and transcription. Previous studies have provided robust evidence that extracellular/circulating miRNAs are biomarkers for disease and play a role in intracellular communication. MiRNAs appear to have a hormone-like activity on cells when it is extracellular/circulating. Of important note, these studies were done in vitro, and further in vivo studies are needed to confirm the findings. However, this is what we understand about miRNAs extracellular/circulating role at this time.
Since their discovery, miRNAs have been shown to be critical regulators of the immune response. Considering periodontal disease is essentially the hosts response to a pathogen, the role of miRNAs in the onset and progression of periodontal disease is of great interest. By modulating protein expression, rather than just switching them on and off, miRNAs affect target gene expression. In short, “during immune and inflammatory responses, miRNAs target inflammatory regulators and affect the magnitude of the inflammatory response.” 
Therefore, miRNAs play a role in cellular function during disease progression. An example would be the dysregulation seen in miRNAs in infectious disease, autoimmune diseases, chronic inflammatory diseases, cardiovascular disorders, nervous system disorders and other diseases. The dysregulation of miRNA found in fluids such as serum, saliva, and gingival crevicular fluid serves as a biomarker for disease. By manipulating miRNA expression, there may be a way to create a targeted therapeutic treatment for multiple pathological conditions that lead to human diseases. 
miRNAs as biomarkers for periodontal disease
More than 600 different miRNAs have been identified in both healthy and periodontally involved patients. Of these 600 miRNAs, miR-223 was most highly expressed and was upregulated in patients with periodontal disease. Interestingly, miR-223 is dysregulated in liver disease, cardiovascular disease, diabetes and multiple different types of cancer. Though its simply an observation I’m projecting, but miR-223 may be a link that needs to be explored further that may explain the connection between periodontal disease and many of the other disease associated with miR-223. Additionally, miR-223 plays an important role in osteoclast formation and the regulation of bone remodeling which is obviously a concern regarding periodontal disease. This discovery of the upregulation of miR-223 may hold potential as a biomarker for periodontal disease that could provide early detection and guide treatment planning for better maintenance. [2-4]
miRNA as a Potential Therapy for Treating Periodontal Disease
The idea of harnessing miRNA as a therapeutic treatment for disease is not new. For several years researcher have been working on using miRNA to treat hepatitis. Specifically, they are targeting miR-122 as it regulates the viral life cycle. Studies in mammals have shown chemical inhibitors of miR-122 reduces the viral load of HCV in infected mammal without causing adverse effects on the liver physiology. 
According to Luan et al. (2018) there are two mechanisms involved in alterations to miRNAs upon infection with oral pathogens, 1) pathogen encoded miRNAs designed to mimic host miRNAs to aid pathogen reproduction and survival and 2) changes in host miRNA expression levels as part of the host immune response. Therefore, it is postulated that altering the expression of core miRNAs may reverse or slow the progression of periodontal disease.
This may seem far-fetched, however in preclinical trials modulating immune checkpoints in murine models afflicted with glioma, showed the augmentation of a particular miRNA (miR-138 via IV delivery) suppressed the growth of glioma cells and prolonged the survival of the animal. 
The authors conclude by stating, “Future research will identify unique combinations and dosages of miRNAs in combination with suitable carrier vehicles and delivery strategies to optimally combat and reverse periodontal disease.”
Personally, I feel miRNA therapeutics are an exciting area of study that could potentially serve to reverse or slow the progression of multiple diseases including periodontal disease. My fear is that the misconception or lack of understanding regarding miRNA therapeutic science will deter some individuals from utilizing this therapy. The vast misunderstanding of the mRNA vaccines produced for COVID-19 is the reason I feel this way. Therefore, by writing this post I hope to encourage those of you in healthcare to learn more regarding this therapy as to better educate and reassure patients in the event it becomes an option for treating disease. It will take a village to combat the misinformation that will likely surround this therapy as more research is published.
1. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018 Aug 3;9:402. doi: 10.3389/fendo.2018.00402. PMID: 30123182; PMCID: PMC6085463. Retrieved from https://www.frontiersin.org/articles/10.3389/fendo.2018.00402/full
2. Luan X, Zhou X, Naqvi A, Francis M, Foyle D, Nares S, Diekwisch TGH. MicroRNAs and immunity in periodontal health and disease. Int J Oral Sci. 2018 Aug 6;10(3):24. doi: 10.1038/s41368-018-0025-y. PMID: 30078842; PMCID: PMC6080405. Retrieved from https://www.nature.com/articles/s41368-018-0025-y
3. Ye D, Zhang T, Lou G, Liu Y. Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med. 2018 Sep 26;50(9):1-12. doi: 10.1038/s12276-018-0153-7. PMID: 30258086; PMCID: PMC6158210. Retrieved from https://www.nature.com/articles/s12276-018-0153-7
4. Taïbi F, Metzinger-Le Meuth V, Massy ZA, Metzinger L. miR-223: An inflammatory oncomiR enters the cardiovascular field. Biochim Biophys Acta. 2014 Jul;1842(7):1001-9. doi: 10.1016/j.bbadis.2014.03.005. Epub 2014 Mar 18. PMID: 24657505. Retrieved from https://www.sciencedirect.com/science/article/pii/S0925443914000659
5. Jopling CL. Targeting microRNA-122 to Treat Hepatitis C Virus Infection. Viruses. 2010;2(7):1382-1393. doi:10.3390/v2071382. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185717/