TABLE 6.

Function of circRNAs in periodontal tissues and cells

CircRNA	miRNA	Target	Function	Cell/tissue Type	Study method
hsa_circ_0081572 (circSERPINE1)	miR‐378h	RORA	Downregulated in periodontitis Enhance viability, suppress apoptosis, inflammatory response, and oxidative stress to inhibit the progression of periodontitis via miR‐378h/RORA axis	Human gingival tissues hPDLSCs	RT‐qPCR, CCK‐8 assay, flow cytometry, Western blot; Caspase 3 activity assay; ELISA; ROS level detection; dual‐luciferase reporter assay, RIP, RNA pulldown assay
hsa_circ_0085289 (circCTHRC1)	let‐7f‐5p	SOCS6	Downregulated in periodontitis Promote cell viability Suppress proinflammatory cytokines production and apoptosis Alleviate injury of hPDLSCs via let‐7f‐5p/SOCS6 axis in response to LPS	Human PDL tissues hPDLSCs	RT‐qPCR, ELISA, cell viability assay, Caspase 3 activity assay; flow cytometry, Western blot; dual‐luciferase reporter assay, RNA pulldown assay, RIP
hsa_circ_002284 (circMAP3K11)	miR‐511‐3p	TLR4	Upregulated in periodontitis Promote the cell viability, proliferation, migration and the osteogenic potential Reduce cell apoptosis Promote the proliferation and inhibit the apoptosis of hPDLSCs via miR‐511‐3p/TLR4 axis in vivo	Human PDL tissues hPDLSCs Periodontitis murine model	Immunohistochemistry assay, target prediction, cell viability assay, cell proliferation assay, cell migration assay, cell apoptosis assay, RT‐qPCR, Western blot, dual‐luciferase reporter assay, TUNEL assay, and Ki‐67 assay in vivo
hsa_circ_0003948 (circKDELR2)	miR‐144‐3p	NR2F2	Downregulated in periodontitis Promote cell proliferation and inhibit apoptosis in response to LPS treatment via miR‐144‐3p/NR2F2/PTEN axis	Human gingival tissues hPDLSCs	RNA‐sequencing, RT‐qPCR, cell proliferation assay, bioinformatic analyses, cell apoptosis assay, dual‐luciferase reporter assay
circ‐Amotl1	miR‐17‐5p	STAT3, Dnmt3a, Fibronectin	Promote skin wound healing in vivo Promote Stat3 expression and facilitate Stat3 nuclear translocation Promote cell adhesion, migration, proliferation, survival, and wound repair of fibroblasts	Human gingival fibroblast cell line (CRL‐2014) NIH 3T3 fibroblast cell line Full‐thickness excisional wound murine model	Wound healing experiment in vivo, cell adhesion and migration assays, cell proliferation and survival assays, ChIP, Western blot, RT‐qPCR, RNA pulldown assay, FISH, dual‐luciferase reporter assay
circ_0138959	miR‐527	CASP5	Upregulated in periodontitis Suppress cell viability and increase pyroptosis in response to LPS via miR‐527/CASP5 axis Promote the secretion of LDH, IL‐1β, and IL‐18, and increase the protein levels of pyroptosis‐related proteins, including caspase‐1, caspase‐4, and GSDMD‐N	Human PDL tissues Human gingival fibroblasts (HGFs)	RT‐qPCR, CCK‐8 assay, LDH measurement, ELISA, flow cytometry, Western blot, dual‐luciferase reporter assay, RNA pulldown assay
hsa_circ_0003489 (circCDK8)	/	mTOR signaling	Upregulated in periodontitis Inhibit the osteogenic differentiation of hPDLSCs by triggering autophagy activation and apoptosis through mTOR signaling in a hypoxic microenvironment	Human PDL tissues hPDLSCs	RT‐qPCR; Western blot; transmission electron microscopy; immunofluorescence analysis; cell apoptosis assay; cell proliferation assay
CDR1as	miR‐7	GDF5/SMAD and p38 MAPK signaling pathway	Upregulated during osteogenic differentiation Promote osteoblastic differentiation of hPDLSCs via miR‐7/GDF5/SMAD and p38 MAPK signaling pathway in vitro and in vivo	hPDLSCs Critical‐sized calvarial defect murine model	RNA oligoribonucleotides, ALP staining and activity assay, ARS staining and quantification, RT‐qPCR, Western blot, dual‐luciferase reporter assay, bone formation assay in vivo, micro‐CT, H&E staining, immunofluorescence staining analysis
CDR1as	miR‐7	ERK signal pathway	Downregulated in periodontitis Regulate the proliferation of hPDLSCs under an LPS‐induced inflammatory condition via miR‐7/ERK signal pathway	Human PDL tissues hPDLSCs	RT‐qPCR, cell proliferation assay, Western blot
CDR1as	miR‐7	KLF4	Upregulated in response to hnRNPM Maintain stemness of hPDLSCs, including expression levels of stemness‐associated genes (SOX2, OCT4, and Nanog), osteogenic differentiation, adipogenic differentiation and migration via miR‐7/KLF4 axis	hPDLSCs	Osteogenic induction, ALP, and alizarin red staining, Adipogenic induction, Oil Red O staining, RT‐qPCR, cell proliferation assay, cell migration assay, RNA pulldown assay, dual‐luciferase reporter assay

Abbreviations: CCK‐8, Cell counting kit‐8; ChIP, chromatin immunoprecipitation; ELISA, enzyme‐linked immunosorbent assay; FISH, florescent in situ hybridization; H&E staining, hematoxylin and eosin staining; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; PDL, periodontal ligament; RIP, RNA immunoprecipitation.