Table 2.

Expression of circRNAs in human periodontal ligament stem cells (hPDLSCs).

Reference	circRNA Name (Gene Name), Genome Location and Length	circRNA Target or Pathway	CircRNA Detection Method	Cell (Tissue) Details	Key Findings
Xie et al. 2021. [54]	hsa_circ_0087960 (LPAR1) chr9:113734352-113735838; 1486 bp hsa_circ_0000437 (CORO1C) chr12:109046047-109048186; 2139 bp hsa_circ_0000448 (GCN1L1) chr12:120592773-120593523; 750 bp	miRNA TGF/β, MAPK, mTOR, and FOXO1 pathways	RNA sequencing RT-qPCR	Human Periodontal Ligament Stem Cells (hPDLSCs) from third molar tissue; Donor ages 18–30 yrs; Passage 3.	69–557 exosomal circRNAs were detected after 5 and 7 days of osteogenic differentiation of hPDLSCs. Exosomal circRNA-LPAR1 was increased and has_circ_0000448 was decreased in hPDLSCs after 5 and 7-days osteogenesis. Function as miRNA sponge and modulate TGF- β, MAPK, mTOR, and FOXO1 pathways.
Wang et al. 2018. [55]	CircRNA3140 CircRNA436	miR-21 miRNA-107 miRNA-335	RT-qPCR RNA sequencing	hPDLSCs; Middle third root; Healthy PDL cells culture; age 14–16 passage 3	1191 cricrRNAs in hPDLSC were enhanced by mechanical force-induced osteogenic differentiation. Potential functions of circRNAs through circRNAs–miRNAs networks. For instance, circRNA3140 targets miR-21; circRNA436 targets miRNA-107 and miRNA-335.
Li et al. 2018. [56]	CDR1as hsa_circ_0001946; chrX:139865339-139866824; 1485 bp	miR-7; TGF-β/Smad and MAPK pathway	RT-qPCR	hPDLSCs PDL tissue from healthy premolars; Passage 4	CircRNA CDR1as inhibits osteogenic differentiation of hPDLSCs via inhibiting miR-7, TGF-β/Smad and MAPK pathways; In vivo knockdown of CDR1as reduced bone formation in a mouse calvarial defect model.
Zheng et al. 2017. [57]	CircCRKL, CircRIMS1, CircMAN1A2, CircETFA	miRNA sponge	RT-qPCR RNA sequencing	hPDLSCs (n = 3) PDL tissue from a healthy premolar; Donor age: 12–18; Passage 4	12,693 circRNA transcripts were detected in hPDCSc osteogenic differentiation with a time-specific expression. Four circRNAs were increased in hPDLSCs osteogenesis by RNA-seq and RT-qPCR; circRNA-miRNA-mRNA network is the potential regulatory role of circRNA.
Gu et al. 2017. [58]	Upregulated: CDR1as, circNCOA3 and circSKIL; Downregulated: circIFF01, circNTNG1, circPLOD2, circSMO and circSMURF2	miRNA34a and miRNA146a; MAPK and Wnt pathway	RT-qPCR RNA sequencing	hPDLSCs Donor age:18–20, Passage 3	1456 circRNAs were differentially expressed after 7-day osteogenic differentiated hPDLSCs. CDR1as, circNCOA3 and circSKIL upregulated during osteogenesis of hPDLSCs; CircRNA-miRNA-mRNA network is the potential function of circRNA in hPDLSCs osteogenic differentiation. For instance, circRNA BANP and circRNA ITCH were predicted to interact with miRNA34a and miRNA146a to regulate PDLSC osteogenic differentiation via the MAPK pathway.

Abbreviations: LPAR1: lysophosphatidic acid receptor 1; CORO1C: coronin 1C; GCN1L1: general control of amino-acid synthesis 1-like 1; CDK8: Cyclin-Dependent Kinase 8; CDR1as: Cerebellar degeneration-related protein 1 antisense RNA; CRKL: CRK Like Proto-Oncogene, Adaptor Protein; RIMS1: Regulating Synaptic Membrane Exocytosis Protein 1; MAN1A2: Mannosyl-oligosaccharide 1; ETFA: Electron Transfer Flavoprotein Subunit Alpha; NCOA3: Nuclear Receptor Coactivator 3; SKIL: The human SKI-like; IFF01: Intermediate Filament Family Orphan 1; NTNG1: Netrin G1; PLOD2: Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2; SMO: Smoothened; SMURF2: SMAD Specific E3 Ubiquitin Protein Ligase 2; BANP: B-cell translocation gene 3 associated nuclear protein; ITCH: Itchy E3 Ubiquitin Protein Ligase; TGF-β: Transforming Growth Factor Beta; MAPK: Mitogen-activated protein kinases; mTOR: mammalian Target of Rapamycin; FOXO1: Forkhead box protein O1; Smad: homologues of the Drosophila protein, mothers against decapentaplegic (Mad) and the Caenorhabditis elegans protein Sma; and Wnt: Wingless-related integration site.