Table 3.

Role of circRNAs expression in the differentiation of human dental pulp stem cells (hDPSCs).

Reference	circRNA Name (Gene Name), Genome Location and Length	circRN Target or Pathway	CircRNA Detection Method	Cell (Tissue) Details	Key Findings
Ji et al. 2020. [59]	circRNA124534/ hsa_circ_0124534 (FRMD4B) chr3:69247848-69265490; 17,642 bp	As a miRNA sponge; miR-496/β-catenin pathway	RT-PCR	hDPSCs healthy pulp tissues (3 male, 3 female); Donor age: females: 22–33; males: 26–41 passage 4	CircRNA124534 enhanced in vitro osteogenic differentiation in hDPSCs via the miR-496/β-catenin pathway. Over-expression of circRNA124534 in vivo increased bone formation in a mouse subcutaneous model.
Chen et al. 2020. [60]	hsa_circRNA_104101	Wnt and the TGF-β signalling pathway	RT-qPCR Microarray Electro-phoresis	hDPSCs donor age:  18–25 yrs; passages 3–5	43 upregulated and 144 downregulated circRNAs were detected in hDPSCs during odontogenic differentiation. hsa_circRNA_104101 promoted hDPSCs odontogenic differentiation.
Ji et al. 2020. [61]	hsa_circ_0026827 (RPL41); chr12:56510373-56511616; 1243 bp	miR-188-3p; Beclin1& RUNX1 pathway	Microarray RT-qPCR	hDPSCs	has_circ_0026827 was upregulated during osteogenic differentiation in hDPSCs. has_circ_0026827 targets the miR-188-3p via Beclin1 & RUNX1 pathway. Overexpression of has_circ_0026827 promoted in vivo bone formation. circRNA–miRNA–mRNA networks may operate during odontogenic differentiation in hDPSCs via the Wnt and TGF-β signalling pathways.
Xie et al. 2020. [62]	circLPAR1 (hsa_circ_0003611) chr9:113703700-113735838; 32,138 bp	hsa-miR-31 SATB2 and RUNX2	RNA-seq RT-PCR	hDPSCs (Exosomes) from one healthy donor (age: 20 yrs); Passage 2	Exosomal crcLPAR1 enhanced osteogenic differentiation of hDPSCs by binding to has-miR-31.
Ge et al. 2020. [63]	circSIPA1L1	miR-617 Smad3	RT-PCR	hDPSCs Third molar from a healthy donor aged 18–25 yrs; Passage is unclear	CircSIPA1L1 promoted osteogenesis via regulating the miR-617 and Smad3 pathway in hDPSCs.
Zhang et al. 2020. [64]	circAKT3 (hsa_circ_0000199) chr1:243708811-243736350; 27,539 bp	miR-206; CX34	qPT-PCR RNA sequencing	hDPSCs premolars and third molars; age:14–25; passages 3 to 5	29 circRNAs were down-regulated and 57 circRNAs were upregulated during hDPSCs osteogenesis. CircAKT3 promoted osteogenesis in hDPSCs by binding to miR-206. In vivo—silencing circAKT3 inhibited bone formation in a mouse subcutaneous model.
Li et al. 2019. [65]	hsa_circ_0015260 (C1orf9), chr1:172520652-172548407; 27,755 bp hsa_circ_0006984 (ZNF79) chr9:130206308-130207528; 1220 bp	miR-135b; MAPK pathway	RT-qPCR RNA-seq	Human dental pulp cells (hDPCs) from healthy premolars and third molars (3 males and 5 females; 12–25 yrs); Passage 3	1341 increased circRNAs and 1780 decreased circRNAs were identified in hDPCs during odontogenic differentiation. Has_circ_0015260 and has_circ_0006984 were up-regulated during osteogenesis of hDPCs via miR-135b and the MAPK pathway.

Abbreviations: FRMD4B: FERM Domain Containing 4B; RPL41: Ribosomal Protein L41; LPAR1: Lysophosphatidic Acid Receptor 1; SIPA1L1: Signal Induced Proliferation Associated 1 Like 1; AKT3: AKT Serine/Threonine Kinase 3; AKT Serine/Threonine Kinase 3: Chromosome 1 open reading frame 9; ZNF79 Zinc Finger Protein 79; CX43: Connexion 43; TGF-β: Transforming growth factor beta 1; RUNX1: runt-related transcription factor 1; SATB2: Special AT-rich sequence-binding protein 2; RUNX2: Runt-related transcription factor 2; Smad3: SMAD family member 3; and MAPK: Mitogen-activated protein kinase.