TABLE 1.

Expression of circadian clock in oral-craniofacial tissue.

Circadian clock genes	Associated tissues	Molecular functions	Animal models/Cell lines	Health	Disease	Related dysregulation/diseases
Clock	Teeth	Amelogenesis and dentinogenesis	Ameloblast cell line LS8	↑	↓	Enamel abnormality (Chen et al., 2020; Zheng et al., 2022)
		Dental pulp cells and dental pulp-derived cells development
		Influences the rhythmic expression of ameloblast-specific genes and Runx2	Dental mesenchyme cell	↑	↓
	Periodontal tissues	Maintains PDL stability				Not retrieved
		Stimulates SMAD3 promotor activity
	Maxillomandibular Complex	Maintains maxillomandibular complex homeostasis	Mice			Not retrieved
		Regulates the maxillomandibular development	Mice
	Oral mucosa	Maintain oral mucosa homeostasis				HNSCC (Li et al., 2016b; Hsu et al., 2014)
		Marker of good prognosis in HNSCC patients	Patients and healthy subjects	↑	↓
Bmal1	Teeth	Bmal1 promotes cementoblast differentiation and cementum mineralization via Wnt/β-catenin signaling	Murine Cementoblast cell line OCCM-30	↑	↓	Defective amelogenesis (Lu et al., 2008), Dentinogenic differentiation disorder (Xu et al., 2022; Hsu et al., 2014)
		Ameloblasts and odontoblasts	Ameloblast cell OCCM-30	↑	↓
		Contributes to the incremental lines of dentin and enamel	Mice	↑	↓
		Affects dentinogenic differentiation of DPSCs via PI3K/Akt/mTOR pathway	DPSCs	↑	↓
		Affects the ameloblast-specific genes Amelx and Klk4 expression
	Periodontal tissues	Maintain gingiva and PDL stability and modulated by hypoxic condition	PDLs	↑	↓	Periodontitis (Tonna et al., 1987; Li et al., 2018; Roestamadji et al., 2019; Deng et al., 2020; Xie et al., 2020; Sehirli et al., 2021)
		Promotes SIRT1/NAD + dissociation and NF-κB transcriptional activity during the inflammatory processes	Mesenchymal stem cells
		Correlated with interalveolar septum resorption	Mice PDLs	↑	↓
	Maxillomandibular Complex	Force-induced expression of BMAL1 in PDLCs is closely involved alveolar bone remodeling	PDLCs	↑	↓	Skeletal mandibular hypoplasia (Zhou et al., 2018) Maxillofacial deformities (Yu et al., 2020; Ma et al., 2019; Min et al., 2016; Xie et al., 2022)
		Bmal Regulation of the Osteogenic Differentiation and Proliferation Via Wnt/β-catenin Pathway	Mouse BMSCs MC3T3-E1 cells Mandibular condylar chondrocyte	↑	↓
		Regulates OPG, MMP3 expression through P65 signaling, resulting in osteogenesis	Rat BMSCs Human/Mice	↑	↓
	Oral mucosa	Elevates the sensitivity of cancer cells to paclitaxel, as a chronotherapy timing biomarker in TSCC	Human tongue epithelial tissues/human tongue keratinocytes, SCC9, SCC25, and CAL27 cell lines	↑	↓	OSCC (Bjarnason et al., 2001a) TSCC (Guo et al., 2020)
		Inhibit tumorigenesis and increases paclitaxel sensitivity in TSCC		↑	↓
	Salivary glands	Affects Aqp5 expression level and salivary fluid secretion/Alter saliva flow	Human, Mice	↑	↓	Sjogren’s syndrome (Zheng et al., 2012; Papagerakis et al., 2014a)
Per1/2/3	Teeth	Contributes to dental differentiation		↑	↓	Defective dentin mineralization (Tao et al., 2016), (Huang et al., 2021)
		Odontoblasts in crown and root	Mice
		Ameloblasts and dental pulp cells	Mice
		Regulates ameloblast differentiation via the PPARγ/AKT1/β-catenin signaling axis	ameloblast-lineage cells (ALCs)
	Periodontal tissues	Periodontal ligament cells and gingival fibroblasts	Periodontal ligament cells			Not retrieved
		Maintain oral mucosa homeostasis
	Salivary glands	Alters Saliva flow				Not retrieved
	Oral mucosa	Modulate cell proliferation, apoptosis and cell cycle progression Associated with carcinogenesis and later cancer stages; Perl via the AKT/mTOR pathway promotes OSCC progression; Regulation of the cycle in CDK/CKI cell cycle network in OSCC; Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PDNAKT/mTOR pathway Associates with tumor development stage in HNSCC	Human tongue epithelial tissues/human tongue keratinocytes, SCC9, SCC25, and CAL27 cell lines	↑	↓	OSCC (Guo et al., 2020; Chen et al., 2012) HNSCC (Gery et al., 2006; Bjarnason et al., 2001a)
Cry1/2	Teeth	Ameloblasts, odontoblasts and dental pulp cells				None reported
		Regulated by hypoxic condition
	Periodontal tissues	Fibroblasts of human gingiva and periodontal ligament				Not retrieved
	Oral mucosa	Modulate cell proliferation, apoptosis and cell cycle progression	Human tongue epithelial tissues/human tongue keratinocytes, SCC9, SCC25, and CAL27 cell lines	↑	↓	OSCC (Guo et al., 2020)
REV-ERBs	Periodontal tissues	Nuclei of cementoblasts around cellular cementum. REV-ERBs activation inhibits proliferation but promotes migration of cementoblast	Cementoblast cell line OCCM-30	↑	↓	None reported
	Teeth	Dental pulp-derived stem cells