Table 2.

Specific miRNAs with reported roles in periodontal inflammation

miRNA	Differential regulation in ‘diseased’ vs. ‘healthy’ gingival tissues	Reported function	Comment
Let-7i	Upregulated	Targets TLR4
miR-16	Upregulated	Activated by p53, facilitates cell cycle arrest and apoptosis
miR-29a	Upregulated	Downregulates IL-23 by targeting IL12p40 and p19; inhibits both intrinsic and extrinsic apoptosis; hypoxamir, induces angiogenesis in hypoxia; mediates osteoblast differentiation by targeting Wnt signaling inhibitors
miR-30e	Downregulated	Inhibits NK cell cytotoxicity
miR-31	Downregulated	Targets a negative regulator of NF-kB; mediates osteoclastogenesis and represses osteogenesis by targeting Osterix
miR-125-3p	Upregulated	Activates p53, pro-apoptotic
miR-141	Downregulated	Targets MAP4K4 (a direct inducer of MAP kinase signaling) and SDF- 1/CXCL12 (mediator of leukocyte migration)
miR-146a	Upregulated	NF-kB dependent miRNA that targets TLR4, IRAK1/TRAF4; increases DC survival by reducing their cytokine production; regulates B cell development, ‘brake’ on autoimmunity; activated by periodontitis-associated TF Bob1	Critical for steering TLR sensitivity
miR-148a	Upregulated	Impairs innate response and antigen presentation of DCs; targets anti- apoptotic Bcl2; mediates osteoclastogenesis
miR-155	Upregulated	miRNA that targets NF-kB signaling; activated by NF-kB, fos/jun, NOD2 signaling, mediates type 1 interferon response to infection; activates PI3K/Akt pathway; induces activation of NK cells; critical for DC maturation and function; essential for Th17 response and T cell development; inhibits DNA damage-induced apoptosis; hypoxamir that triggers cell cycle arrest, induces autophagy and targets HIF-1α in hypoxia (pro- survival); induced by adiponectin stimulation	Critical for steering TLR sensitivity, directly affects expression level of other miRNAs; miR-155 targeting improves chronic inflammatory diseases
miR-185	Upregulated	Enhances DNA damage-induced apoptosis
miR-200a	Downregulated	Negatively regulates IL-12 signaling in NK cells
miR-200c	Downregulated	Targets TLR4; targets pro-apoptotic Noxa and anti-apoptotic FAP-1; inhibits endothelial cell differentiation and angiogenesis; induces osteoclastogenesis
miR-203	Downregulated	Targets VEGFA, inhibiting angiogenesis
miR-210	Downregulated	Impairs immune-suppressive functions of Tregs by targeting FOXP3; hypoxamir, controls host responses in hypoxia by induction of autophagy and targeting of HIF-1α (pro-survival)
miR-451	Upregulated	Suppresses neutrophil chemotaxis via p38 MAPK; reduces cytokine secretion in DCs	Dicer-independent miRNA
miR-486	Upregulated	Disrupts NF-kB negative feedback loops, leading to stronger NF-kB activation
miR-497	Upregulated	Facilitates intrinsic apoptosis
miR-650	Upregulated	Regulates B cell proliferation by targeting CDK1