The Genes Involved in Dentinogenesis

Figures & data

Table 1. The genes involved in dentinogenesis

Pathway	Gene	Main function in dentinogenesis
Extracellular matrix proteins and related	COL1A1/2, COL2A1, COL4A1/2/3/4/5/6	The COL1A1/2 ^Citation2,Citation3 and COL2A14 mutation results in dentinogenesis imperfecta; Type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation.5
	DSPP, DPP, DSP, DGP	Dentin hypoplasia or dysplasia. It is an important marker of odontoblast.^Citation6
	DLX3	Deletion of Dlx3 leads to major dentin defects through down-regulation of Dspp.^Citation7
	TM14	Mainly expressed in odontoblasts,and participates in the formation and mineralization of dentin.^Citation8
	BSP	As the crystal nucleus, promotes the crystal formation, and participate in dentinogenesis.^Citation9
	Dmp1/2/3/4	Dmp1/2 participates in the differentiation and dentin formation of odontoblasts.^Citation10,Citation11 Rat Dmp3 is a compound protein of rat DSP and phosphophoryn.^Citation12 Dmp4 forms and affects the growth and arrangement of hydroxyapatite crystals, and promotes the differentiation of osteoblasts, ameloblasts and odontoblasts.^Citation13
	EMILIN-1/2/3	EMILIN-1 and −2 staining appears to increase in the pre-dentin and in the ECM surrounding odontoblasts. EMILIN-3 was significantly increased in inflamed odontoblasts.^Citation14
	SSUH2	Decrease of collagen in the teeth of mice, which makes the dentin mineralization abnormal.^Citation15
	GRP78	SSUH2 binds to the Dank domain of GRP78 through DanJ, which affects the transport of collagen and DMP1, there by affecting the mineralization of teeth.^Citation16
	Sulf1/2	Sulf1/Sulf2 double null mutant mice exhibit a thin dentin matrix and short roots.^Citation17
	MMP1/2/7/8/9/10/11/13/14/15/16/17/19/20/23/24/25	MMP1 regulate tooth agenesis; MMP2 makes multiple cleavages near the DSP C terminus, releasing larger forms of DGP; MMP8 may be involved in the alteration of dentin matrix during the development of human and rat tooth germ; MMP9 is important for tooth development and DSP is a target of MMP9 during dentinogenesis; MMP14 functions in tooth root formation, dentinogenesis, and tooth eruption; MMP-20 cleaves DSP-DGP to generate DSP and DGP; MMP1, 2, 9, 10, 11, 13, 14, 15, 16, 17, 19, 20, 23, 24 and 25 expressed in odontoblasts.^Citation18–20
	TIMP1/2/3	Expression was detected in odontoblasts.^Citation21
	Osteocalcin	Both crown and root odontoblasts and dentin stained for Osteocalcin.^Citation20
	Osteonectin	Osteonectin was present mostly in the nonmineralized predentin.^Citation22
	MEPE	It plays an important role in the formation of dentinal tubules and pulpal homeostasis.^Citation23
	PHEX	A decrease in PHEX expression could suppress dentin formation.^Citation24
	Versican, Decorin, Appican, Biglycan, Glypican, Syndecan-1/3	Decorin, biglycan, syndecan-1 and syndecan-3 showed gene expressions overlapping with OASIS. Especially the expression pattern of decorin and syndecan-3 coincided temporally and spatially exactly with that of OASIS.^Citation25
	Tenascin	Association with dentinal tubules, particularly prominent in the tooth crown.^Citation26
	Tuftelin	Tuftelin could be secreted by preodontoblast cells and preameloblast cells.^Citation27
	Reelin	Reelin may promote adhesion between dental nerve endings and odontoblasts.^Citation28,Citation29
	S100-A7	S100-A7 released from dentin by MMP20 might play a key role in dentin pulp regeneration.^Citation30
Mineralization related pathway	Bono1	Expressed in functional odontoblasts and was associated with regions of matrix mineralization.^Citation31
	Runx2	Participation in dentin formation, mineralization, and development of odontoblasts.^Citation32
	Msx2	Msx2 expressed in the odontoblast.^Citation33
	PAX9	Tooth agenesis.^Citation34
	Opn	Essential for type I collagen secretion in reparative dentin.^Citation35
	Vdr	Vitamin D receptors deficiency compromises dentin maturation.^Citation36
	Smpd3	Deletion of smpd3 induces dentinogenesis imperfecta in mice.^Citation37
	Osad	Osad may play an important role during tooth development and biomineralization of dentin.^Citation38
	SOST	Sclerostin deficiency hastened reparative dentinogenesis after pulp injury.^Citation39
	ANKH	Direct mineralization in cementum and likely other mineralized tissues.^Citation40
	OSX	Involved in the differentiation, maturation and intercellular signal transduction of odontoblasts.^Citation41
	SMOC2	Dentin dysplasia, small teeth, missing teeth.^Citation42
	CCN2	Associated with reparative dentinogenesis.^Citation43
	PACE4	PACE4 plays a crucial role in dentinogenesis, especially via the activation of BMPs.^Citation44
	Alp/Alpl	Tooth mineralization.^Citation45
	RANK/RANKL	Associated with delayed permanent tooth emergence and tooth development.^Citation46
	OPG	Resulted in reduced mineralization.^Citation46
Wnt Signaling Pathway	Timp1	Play crucial roles in reactivation of immature pulp cells for tertiary dentinogenesis.^Citation47
	CTNNB1	Tooth agenesis.^Citation48
	APC	Supernumerary tooth; Odontoma.^Citation49
	Kremen1	Ectodermal dysplasia including oligodontia.^Citation50
	LRP6	Oligodontia.^Citation51
	Axin2	Axin2-expressing cells differentiate into new odontoblast-like cells that secrete reparative dentine.^Citation52
	Ctbp1	Hypotonia.^Citation53
	SFRP2	Key factor in maintaining cell survival following dentinogenic commitment.^Citation54
	Lef1	Play a key role in odontoblast differentiation through regulating Dspp expression.^Citation55
	Wnt1/2/3a/4/5a/5b/6/7a/7b/8a/8b/9b/10a/10b/11/13/14/16	Tooth agenesis.^Citation56,Citation57 mediation of dentinogenesis.^Citation58,Citation59
	VPS4B	Regulate tooth development.^Citation60
Shh Signaling Pathway	Shh	Shh regulates growth and determines the shape of the tooth.^Citation61
	Ptch1/2	Regulate teeth stem cell maintenance and differentiation.^Citation62
	MSX1/2	Msx1 and Msx2 play a major role in tooth formation.^Citation63
	Gli1/2/3	Gli1^+ cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. Gli2 mutants were found to have abnormal development of maxillary incisors, whereas Gli3 mutants had no major tooth abnormalities. Gli2/Gli3 double homozygous mutants did not develop any normal teeth.^Citation64,Citation65
	Sufu	Modulating the tooth germ morphogenesis during the bud-to-cap stage transition.^Citation61
	Nfic	Nfic has an essential role in tooth root formation.^Citation66
	Kif3a	Kif3a-deficient mice results in tooth dysplasia.^Citation67
TGFβ Signaling Pathway	TGF-β	Matrix formation and pulpal obliteration.^Citation68
	Activin βA	Activin βA by follistatin may allow odontoblast terminal differentiation to occur.^Citation69,Citation70
	Follistatin	Activin-follistatin system regulates odontoblast differentiation during tooth development.^Citation69
	Islet1	Exclusively expressed in epithelial cells of the developing incisors during odontogenesis.^Citation71
	Ectodin	Ectodin inhibited the activity of BMP2, BMP4, BMP6, and BMP7.^Citation72
	BMP1/2/3/4/5/7/9	Play a crucial role in organogenesis, including tooth development.^Citation73,Citation74 Participates in the process of cell differentiation, mineralization and dentinogenesis.^Citation75
	KLF4	Klf4 promotes dentinogenesis and odontoblastic differentiation via modulation of TGF-β signaling pathway and interaction with histone acetylation.^Citation22
	p300, HDAC3	p300- and HDAC3-regulated odontoblast differentiation through upregulating histone acetylation.^Citation76
Notch Signaling Pathway	Notch 1/2/3	Upregulation of Notch signaling pathway after tooth injury.^Citation77
	TSPEAR	Mutations in TSPEAR, encoding a regulator of Notch signaling, affect tooth morphogenesis.^Citation78
	DLK1	Inhibited the odontoblastic differentiation of hDPSCs.^Citation79
TNF Signaling Pathway	Eda, Edar, Edaradd	Tooth agenesis.^Citation80
	Traf6	Regulate cuspal morphogenesis.^Citation81
	TNFRSF19	Expressed in an overlapping domain with Edar in the tooth.^Citation82
Ion channel	Nav1.1/1.2/1.3/1.4/1.5/1.6/1.7/1.8/1.9	Nine voltage-gated sodium channels are all expressed in odontoblasts, and their expression location depends on the tooth position and tooth maturity. Related to tooth sensitivity.^Citation83
	TRPC1/2/3/4/5/6/7	TRPC1-7 belongs to the calcium channel family and were mainly expressed in odontoblasts.^Citation84
	CLCN1/2/3/4/5/6/7	Regulated tooth development through effects on cell proliferation and cell cycle signal pathway.^Citation85
	TRPM3/7/8	Both odontoblasts and dental pulp cells express TRPM channels in rat, mouse and human tooth.^Citation86
	Piezo1/2	Expressed in odontoblasts.^Citation87
	TRPV1/2//3/4	TRPV1/2//3/4 channels expressed in odontoblasts.^Citation88
	P2X3/4/5/7, P2Y1 /2/4/6/11/12/13/14	Extracellular ATP activates P2 receptors and downstream signaling events that induce cell odontogenic differentiation.^Citation89
	AQP4/5	AQP4 and AQP5 immunostaining was observed in the odontoblasts and their processes.^Citation90
	AHR	Tooth mineralization.^Citation91
Growth factor	FGF1/2/3/4/7/8/9/10/11/12/13/15/17/20, FGFR1/2/3	Function in dentinogenesis.^Citation92–96
	COUP-TFII	Matrix mineralization in odontoblast-lineage cells.^Citation97
	β2AR	The sympathetic nervous system decreases tertiary dentin formation via β2AR.^Citation98
	PTH/PTHrP/PTH1R	Essential signal in the formation of the eruption pathway.^Citation99
	IGF-1	IGF-1 can weaken odontogenic differentiation and dentinogenesis capability.^Citation100
	EXT-1	Function in the dentin formation.^Citation101
	Oxytocin	Promote odontoblast-like cell differentiation, resulting in increased dentin formation.^Citation102
	IGFBP5/6/7	IGFBP5/6/7 may play independent and redundant regulatory roles in late-stage odontogenesis.^Citation102
Stress response	HSP25/70	Hsp25 is involved in reinforcement of the cell layer following cell movement during odontogenesis. Hsp70 might play an important role during reparative dentin formation.^Citation103
	Ape1	Promote the odontogenic differentiation capacity.^Citation104
	DRP1	DRP1 inhibition accelerates dentin formation through mitochondrial elongation and activation.^Citation105
	MTCO2	Age-related changes marker in odontoblasts.^Citation106
	PPARα/γ	Active PPARα signaling is required to achieve normal mineralization of molar enamel. PPARγ in pulp cells increases cell viability, odontoblastic differentiation, and dentin mineralization under oxidative stress.^Citation107,Citation108
	LAMP2	Lysosomal (LAMP2) markers, ageing and stress related in odontoblasts.^Citation106
	SIRT4	Sirt4 knockdown resulted in reduced odontogenic differentiation and mineralization.^Citation109
Nervous system related pathway	GDNF	Function in odontoblasts develop, differentiate, and the matrix and predentin layers formation.^Citation110
	Nestin	The original odontoblasts may differently regulate Nestin expression.^Citation111
	NRG-1, ErbB3/4	NRG-1 and the receptors ErbB3/4 are expressed locally during rodent tooth development.^Citation112
	Lhx8	Regulates dentin development and regeneration.^Citation113
Cell junction related genes	OCLN, CLDN1, Zo1/2	Play an important role in the differentiation of odontoblasts.^Citation114
	CNRs, Pcdh-γ, Reelin	Related to both morphogenesis and cell differentiation events.^Citation28
	E-cadherin, P-cadherin	Differential and specific roles for E-cadherin and P-cadherin during the morphogenesis.^Citation115
	Connexin26/32/43	Expressed in odontoblasts.^Citation116
Bile secretion pathway	SLC2A1, SLC4A4, ADCY5, ATP1B1, SLC10A1, ABCC3	Expressed in tooth germ odontoblasts.^Citation117
Other related genes	IFT140	IFT140 is essential in promoting dentin formation and reparation.^Citation118
	EphrinB1, EphB2	Regulates odontogenic differentiation and the early stages of tooth injury.^Citation119
	KDM1A, KDM5A	KDM1A have function for the dentinogenesis.^Citation120 Inhibits the odontogenic differentiation and plays an important role in reparative dentinogenesis.^Citation121
	PrP	Odontoblasts showed prominent staining for PrP at levels comparable to those of nerve fibers.^Citation122
	HtrA1	HtrA1 might positively regulate odontoblastic differentiation.^Citation123
	PP1	PP1 might be a potent regulator of odontoblastic differentiation and dentinogenesis.^Citation124
	Sema3A	Play an important role in dentin regeneration via canonical Wnt/β-catenin signaling.^Citation125
	CPNE7	CPNE7 induced odontoblast differentiation in vitro and promoted dentin formation in vivo.^Citation126
	MAP1B	MAP1B could be involved in the terminal differentiation of odontoblasts.^Citation127
	Phospho1	Function in the early mineralization of mantle dentin.^Citation128
	Midkine	Midkine promotes odontoblast-like differentiation and tertiary dentin formation.^Citation129
	Cdc42	Is particularly required for cell survival and tooth morphogenesis.^Citation130
	Sp1/3/6/7	Sp1 promotes the odontoblastic differentiation and mineralization of dental papilla cells^Citation131; Sp3 is essential for post-natal survival and late tooth development^Citation132; Sp6 has been found to present striking dental abnormalities^Citation133; Sp7 is required for proliferation and differentiation of odontoblasts.^Citation134
	Zeb1	Promoted odontoblast differentiation in the early stage.^Citation135
	Fubp1	Plays a modulating role during dentinogenesis.^Citation136
	GATA4	Important for root formation and odontoblast polarity.^Citation137
	ADAMTS2	Mutation in ADAMTS2 causes multiple tooth agenesis and focal dysplastic dentin defects.^Citation138
	Trps1	Trps1 functions as a repressor of later stages of dentinogenesis.^Citation139
	OASIS	Play an important role in the differentiation of the odontoblast.^Citation25
	Hand2	Essential for odontoblasts cells during development.^Citation140
	RICK	Regulates odontogenic differentiation of dental pulp stem cells.^Citation141
	WWP2	Promotes Odontoblastic Differentiation.^Citation142
	TANGO1	Severe dentinogenesis imperfecta.^Citation143
	Mdm2	Promotes the odontoblast-like differentiation.
	Glut1/2/4	Dentinogenesis.^Citation32,Citation144
	MTOR	Reparative dentinogenesis.^Citation32
	CB1	Enhance the dentinogenic differentiation ability.^Citation145
	Parp-1	Involved in the regulation of continuous dentinogenesis in the incisors at an advanced age.^Citation146
	Usp34	USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.^Citation147,Citation148
	mTORC1	mTORC1 involed in odontoblast proliferation and mineralization.148

Budsamongkol T, Intarak N, Theerapanon T, Yodsanga S, Porntaveetus T, Shotelersuk V. A novel mutation in col1a2 leads to osteogenesis imperfecta/ehlers-danlos overlap syndrome with brachydactyly. Genes Dis. 2019;6(2):138–46. doi:10.1016/j.gendis.2019.03.001.

 PubMed Web of Science ®Google Scholar

Andersson K, Dahllöf G, Lindahl K, Kindmark A, Grigelioniene G, Åström E, Malmgren B. Mutations in col1a1 and col1a2 and dental aberrations in children and adolescents with osteogenesis imperfecta–a retrospective cohort study. PLoS One. 2017;12(5):e0176466. doi:10.1371/journal.pone.0176466.

 PubMed Web of Science ®Google Scholar

Nagai N, Nakano K, Sado Y, Naito I, Gunduz M, Tsujigiwa H, Nagatsuka H, Ninomiya Y, Siar CH. Localization of type iv collagen a 1 to a 6 chains in basement membrane during mouse molar germ development. Int J Dev Biol. 2001;45:827–31.

 PubMed Web of Science ®Google Scholar

Yuan G, Chen L, Feng J, Yang G, Ni Q, Xu X, Wan C, Lindsey M, Donly KJ, MacDougall M. Dentin sialoprotein is a novel substrate of matrix metalloproteinase 9 in vitro and in vivo. Sci Rep. 2017;7:42449. doi:10.1038/srep42449.

 PubMed Web of Science ®Google Scholar

Duverger O, Zah A, Isaac J, Sun H-W, Bartels AK, Lian JB, Berdal A, Hwang J, Morasso MI. Neural crest deletion of dlx3 leads to major dentin defects through down-regulation of dspp. J Biol Chem. 2012;287(15):12230–40. doi:10.1074/jbc.M111.326900.

 PubMed Web of Science ®Google Scholar

De Vega S, Iwamoto T, Nakamura T, Hozumi K, McKnight DA, Fisher LW, Fukumoto S, Yamada Y. Tm14 is a new member of the fibulin family (fibulin-7) that interacts with extracellular matrix molecules and is active for cell binding. J Biol Chem. 2007;282(42):30878–88. doi:10.1074/jbc.M705847200.

 PubMed Web of Science ®Google Scholar

Vijaykumar A, Dyrkacz P, Vidovic-Zdrilic I, Maye P, Mina M. Expression of bsp-gfptpz transgene during osteogenesis and reparative dentinogenesis. J Dent Res. 2020;99(1):89–97. doi:10.1177/0022034519885089.

 PubMed Web of Science ®Google Scholar

Qin C, D’Souza R, Feng J. Dentin matrix protein 1 (dmp1): new and important roles for biomineralization and phosphate homeostasis. J Dent Res. 2007;86(12):1134–41. doi:10.1177/154405910708601202.

 PubMed Web of Science ®Google Scholar

Tompkins K, Alvares K, George A, Veis A. Two related low molecular mass polypeptide isoforms of amelogenin have distinct activities in mouse tooth germ differentiation in vitro. J Bone Miner Res. 2005;20(2):341–49. doi:10.1359/JBMR.041107.

 PubMed Web of Science ®Google Scholar

George A, Srinivasan R, Thotakura SR, Liu K, Veis A. Rat dentin matrix protein 3 is a compound protein of rat dentin sialoprotein and phosphophoryn. Connect Tissue Res. 1999;40(1):49–57. doi:10.3109/03008209909005277.

 PubMed Web of Science ®Google Scholar

Hao J, Narayanan K, Muni T, Ramachandran A, George A. Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation. J Biol Chem. 2007;282(21):15357–65. doi:10.1074/jbc.M701547200.

 PubMed Web of Science ®Google Scholar

Imhof T, Korkmaz Y, Koch M, Sengle G, Schiavinato A. Emilin proteins are novel extracellular constituents of the dentin-pulp complex. Sci Rep. 2020;10(1):15320. doi:10.1038/s41598-020-72123-2.

 PubMed Web of Science ®Google Scholar

Xiong F, Ji Z, Liu Y, Zhang Y, Hu L, Yang Q, Qiu Q, Zhao L, Chen D, Tian Z. Mutation in ssuh2 causes autosomal‐dominant dentin dysplasia type i. Hum Mutat. 2017;38(1):95–104. doi:10.1002/humu.23130.

 PubMed Web of Science ®Google Scholar

Ravindran S, Narayanan K, Eapen AS, Hao J, Ramachandran A, Blond S, George A. Endoplasmic reticulum chaperone protein grp-78 mediates endocytosis of dentin matrix protein 1. J Biol Chem. 2008;283(44):29658–70. doi:10.1074/jbc.M800786200.

 PubMed Web of Science ®Google Scholar

Hayano S, Kurosaka H, Yanagita T, Kalus I, Milz F, Ishihara Y, Islam MN, Kawanabe N, Saito M, Kamioka H. Roles of heparan sulfate sulfation in dentinogenesis. J Biol Chem. 2012;287(15):12217–29. doi:10.1074/jbc.M111.332924.

 PubMed Web of Science ®Google Scholar

Yoshiba N, Yoshiba K, Stoetzel C, Perrin‐Schmitt F, Cam Y, Ruch JV, Lesot H. Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development. Dev Dyn. 2003;228(1):105–12. doi:10.1002/dvdy.10352.

 PubMed Web of Science ®Google Scholar

Xu H, Snider T, Wimer H, Yamada S, Yang T, Holmbeck K, Foster B. Multiple essential mt1-mmp functions in tooth root formation, dentinogenesis, and tooth eruption. Matrix Biol. 2016;52:266–83. doi:10.1016/j.matbio.2016.01.002.

 PubMed Web of Science ®Google Scholar

Papagerakis P, Berdal A, Mesbah M, Peuchmaur M, Malaval L, Nydegger J, Simmer J, Macdougall M. Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth. Bone. 2002;30(2):377–85. doi:10.1016/S8756-3282(01)00683-4.

 PubMed Web of Science ®Google Scholar

Gullard A, Gluhak-Heinrich J, Papagerakis S, Sohn P, Unterbrink A, Chen S, MacDougall M. Mepe localization in the craniofacial complex and function in tooth dentin formation. J Histochem Cytochem. 2016;64(4):224–36. doi:10.1369/0022155416635569.

 PubMed Web of Science ®Google Scholar

Lv H, Fu S, Wu G, Yan F. Phex neutralizing agent inhibits dentin formation in mouse tooth germ. Tissue Cell. 2011;43(2):125–30. doi:10.1016/j.tice.2010.12.008.

 PubMed Web of Science ®Google Scholar

Hikake T, Mori T, Iseki K, Hagino S, Zhang Y, Takagi H, Yokoya S, Wanaka A. Comparison of expression patterns between creb family transcription factor oasis and proteoglycan core protein genes during murine tooth development. Anat Embryol (Berl). 2003;206(5):373–80. doi:10.1007/s00429-003-0311-z.

 PubMedGoogle Scholar

Thesleff I, Mackie E, Vainio S, Chiquet-Ehrismann R. Changes in the distribution of tenascin during tooth development. Development. 1987;101(2):289–96. doi:10.1242/dev.101.2.289.

 PubMed Web of Science ®Google Scholar

Zeichner-David M, Vo H, Tan H, Diekwisch T, Berman B, Thiemann F, Alcocer M, Hsu P, Wang T, Eyna J. Timing of the expression of enamel gene products during mouse tooth development. Int J Dev Biol. 2003;41:27–38.

 Google Scholar

Heymann R, Kallenbach S, Alonso S, Carroll P, Mitsiadis TA. Dynamic expression patterns of the new protocadherin families cnrs and pcdh-γ during mouse odontogenesis: comparison with reelin expression. Mech Dev. 2001;106(1–2):181–84. doi:10.1016/S0925-4773(01)00433-6.

 PubMed Web of Science ®Google Scholar

Maurin J-C, Couble M-L, Didier-Bazes M, Brisson C, Magloire H, Bleicher F. Expression and localization of reelin in human odontoblasts. Matrix Biol. 2004;23(5):277–85. doi:10.1016/j.matbio.2004.06.005.

 PubMed Web of Science ®Google Scholar

Komichi S, Takahashi Y, Okamoto M, Ali M, Watanabe M, Huang H, Nakai T, Cooper P, Hayashi M. Protein s100-a7 derived from digested dentin is a critical molecule for dentin pulp regeneration. Cells. 2019;8(9). doi:10.3390/cells8091002.

 PubMed Web of Science ®Google Scholar

James MJ, Järvinen E, Thesleff I. Bono1: a gene associated with regions of deposition of bone and dentine. Gene Expression Patterns. 2004;4(5):595–99. doi:10.1016/j.modgep.2004.01.013.

 PubMed Web of Science ®Google Scholar

Takeuchi R, Ohkura N, Yoshiba K, Tohma A, Yoshiba N, Edanami N, Shirakashi M, Belal RSI, Ohshima H, Noiri Y. Immunohistochemistry and gene expression of glut1, runx2 and mtor in reparative dentinogenesis. Oral Dis. 2020;26(2):341–49. doi:10.1111/odi.13230.

 PubMed Web of Science ®Google Scholar

Bidder M, Latifi T, Towler DA. Reciprocal temporospatial patterns of msx2 and osteocalcin gene expression during murine odontogenesis. J Bone Miner Res. 1998;13(4):609–19. doi:10.1359/jbmr.1998.13.4.609.

 PubMed Web of Science ®Google Scholar

Wang S-K, Chan H-C, Makovey I, Simmer JP, Hu JC. Novel pax9 and col1a2 missense mutations causing tooth agenesis and oi/dgi without skeletal abnormalities. PLoS One. 2012;7(12):e51533. doi:10.1371/journal.pone.0051533.

 PubMed Web of Science ®Google Scholar

Saito K, Nakatomi M, Ida-Yonemochi H, Ohshima H. Osteopontin is essential for type i collagen secretion in reparative dentin. J Dent Res. 2016;95(9):1034–41. doi:10.1177/0022034516645333.

 PubMed Web of Science ®Google Scholar

Zhang X, Rahemtulla FG, MacDougall MJ, Thomas HF. Vitamin d receptor deficiency affects dentin maturation in mice. Arch Oral Biol. 2007;52(12):1172–79. doi:10.1016/j.archoralbio.2007.06.010.

 PubMed Web of Science ®Google Scholar

Chae Y-M, Heo S-H, Kim J-Y, Lee J-M, Ryoo H-M, Cho J-Y. Upregulation of smpd3 via bmp2 stimulation and runx2. BMB Reports. 2009;42(2):86–90. doi:10.5483/BMBRep.2009.42.2.086.

 PubMed Web of Science ®Google Scholar

Petersson U, Hultenby K, Wendel M. Identification, distribution and expression of osteoadherin during tooth formation. Eur J Oral Sci. 2003;111(2):128–36. doi:10.1034/j.1600-0722.2003.00027.x.

 PubMed Web of Science ®Google Scholar

Collignon A-M, Amri N, Lesieur J, Sadoine J, Ribes S, Menashi S, Simon S, Berdal A, Rochefort G, Chaussain C. Sclerostin deficiency promotes reparative dentinogenesis. J Dent Res. 2017;96(7):815–21. doi:10.1177/0022034517698104.

 PubMed Web of Science ®Google Scholar

Ao M, Chavez M, Chu E, Hemstreet K, Yin Y, Yadav M, Millán J, Fisher L, Goldberg H, Somerman M. Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis. Bone. 2017;105:134–47. doi:10.1016/j.bone.2017.08.027.

 PubMed Web of Science ®Google Scholar

Chen S, Gluhak-Heinrich J, Wang Y, Wu Y, Chuang H, Chen L, Yuan G, Dong J, Gay I, MacDougall M. Runx2, osx, and dspp in tooth development. J Dent Res. 2009;88(10):904–09. doi:10.1177/0022034509342873.

 PubMed Web of Science ®Google Scholar

Morkmued S, Clauss F, Schuhbaur B, Fraulob V, Mathieu E, Hemmerlé J, Clevers H, Koo B-K, Dollé P, Bloch-Zupan A. Deficiency of the smoc2 matricellular protein impairs bone healing and produces age-dependent bone loss. Sci Rep. 2020;10(1):1–14. doi:10.1038/s41598-020-71749-6.

 PubMed Web of Science ®Google Scholar

Muromachi K, Kamio N, Matsuki‐Fukushima M, Nishimura H, Tani‐Ishii N, Sugiya H, Matsushima K. Ccn 2/ctgf expression via cellular uptake of bmp‐1 is associated with reparative dentinogenesis. Oral Dis. 2015;21(6):778–84. doi:10.1111/odi.12347.

 PubMed Web of Science ®Google Scholar

Akamatsu T, Matsuda Y, Tsumura K, Tada J, Parvin MN, Wei W, Kanamori N, Hosoi K. Highly regulated expression of subtilisin-like proprotein convertase pace4 (spc4) during dentinogenesis. Biochem Biophys Res Commun. 2000;272(2):410–15. doi:10.1006/bbrc.2000.2752.

 PubMed Web of Science ®Google Scholar

Mao X, Liu S, Lin Y, Chen Z, Shao Y, Yu Q, Liu H, Lu Z, Sheng H, Lu X. Two novel mutations in the alpl gene of unrelated Chinese children with hypophosphatasia: case reports and literature review. BMC Pediatr. 2019;19(1):456. doi:10.1186/s12887-019-1800-4.

 PubMed Web of Science ®Google Scholar

Ohazama A, Courtney J-M, Sharpe P. Opg, rank, and rankl in tooth development: co-ordination of odontogenesis and osteogenesis. J Dent Res. 2004;83(3):241–44. doi:10.1177/154405910408300311.

 PubMed Web of Science ®Google Scholar

Yoshioka S, Takahashi Y, Abe M, Michikami I, Imazato S, Wakisaka S, Hayashi M, Ebisu S. Activation of the wnt/β-catenin pathway and tissue inhibitor of metalloprotease 1 during tertiary dentinogenesis. J Biochem. 2013;153(1):43–50. doi:10.1093/jb/mvs117.

 PubMed Web of Science ®Google Scholar

Mostowska A, Biedziak B, Zadurska M, Dunin‐Wilczynska I, Lianeri M, Jagodzinski P. Nucleotide variants of genes encoding components of the wnt signalling pathway and the risk of non‐syndromic tooth agenesis. Clin Genet. 2013;84(5):429–40. doi:10.1111/cge.12061.

 PubMed Web of Science ®Google Scholar

Yu F, Cai W, Jiang B, Xu L, Liu S, Zhao S. A novel mutation of adenomatous polyposis coli (apc) gene results in the formation of supernumerary teeth. J Cell Mol Med. 2018;22(1):152–62. doi:10.1111/jcmm.13303.

 PubMed Web of Science ®Google Scholar

Issa YA, Kamal L, Rayyan AA, Dweik D, Pierce S, Lee MK, King M-C, Walsh T, Kanaan M. Mutation of kremen1, a modulator of wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families. Eur J Human Genet. 2016;24(10):1430–35. doi:10.1038/ejhg.2016.29.

 PubMed Web of Science ®Google Scholar

Ockeloen CW, Khandelwal KD, Dreesen K, Ludwig KU, Sullivan R, Van Rooij IA, Thonissen M, Swinnen S, Phan M, Conte F. Novel mutations in lrp6 highlight the role of wnt signaling in tooth agenesis. Genet Med. 2016;18(11):1158. doi:10.1038/gim.2016.10.

 PubMed Web of Science ®Google Scholar

Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P. Mutations in axin2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet. 2004;74(5):1043–50. doi:10.1086/386293.

 PubMed Web of Science ®Google Scholar

Beck DB, Subramanian T, Vijayalingam S, Ezekiel UR, Donkervoort S, Yang ML, Dubbs HA, Ortiz-Gonzalez XR, Lakhani S, Segal D. A pathogenic ctbp1 missense mutation causes altered cofactor binding and transcriptional activity. neurogenetics. 2019;20(3):129–43. doi:10.1007/s10048-019-00578-1.

 PubMed Web of Science ®Google Scholar

Yu G, Wang J, Lin X, Diao S, Cao Y, Dong R, Wang L, Wang S, Fan Z. Demethylation of sfrp 2 by histone demethylase kdm 2a regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla. Cell Prolif. 2016;49(3):330–40. doi:10.1111/cpr.12256.

 PubMed Web of Science ®Google Scholar

Nakatomi M, Ida-Yonemochi H, Ohshima H. Lymphoid enhancer-binding factor 1 expression precedes dentin sialophosphoprotein expression during rat odontoblast differentiation and regeneration. J Endod. 2013;39(5):612–18. doi:10.1016/j.joen.2012.12.016.

 PubMed Web of Science ®Google Scholar

Yamashiro T, Zheng L, Shitaku Y, Saito M, Tsubakimoto T, Takada K, Takano‐Yamamoto T, Thesleff I. Wnt10a regulates dentin sialophosphoprotein mrna expression and possibly links odontoblast differentiation and tooth morphogenesis. Differentiation. 2007;75(5):452–62. doi:10.1111/j.1432-0436.2006.00150.x.

 PubMed Web of Science ®Google Scholar

Kantaputra P, Hutsadaloi A, Kaewgahya M, Intachai W, German R, Koparal M, Leethanakul C, Tolun A, Ketudat Cairns J. Wnt10b mutations associated with isolated dental anomalies. Clin Genet. 2018;93(5):992–99. doi:10.1111/cge.13218.

 PubMed Web of Science ®Google Scholar

Chen D, Yu F, Wu F, Bai M, Lou F, Liao X, Wang C, Ye L. The role of wnt7b in the mediation of dentinogenesis via the erk1/2 pathway. Arch Oral Biol. 2019;104:123–32. doi:10.1016/j.archoralbio.2019.05.009.

 PubMed Web of Science ®Google Scholar

Zeng Y, Baugh E, Akyalcin S, Letra A. Functional effects of wnt10a rare variants associated with tooth agenesis. J Dent Res. 2020;22034520962728.

 Web of Science ®Google Scholar

Pan Y, Lu T, Peng L, Chen Z, Li M, Zhang K, Xiong F, Wu B. Vacuolar protein sorting 4b regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the wnt-β-catenin signalling pathway. Artif Cells, Nanomed Biotechnol. 2019;47(1):2575–84. doi:10.1080/21691401.2019.1629950.

 PubMed Web of Science ®Google Scholar

Li J, Xu J, Cui Y, Wang L, Wang B, Wang Q, Zhang X, Qiu M, Zhang Z. Mesenchymal sufu regulates development of mandibular molars via shh signaling. J Dent Res. 2019;98(12):1348–56. doi:10.1177/0022034519872679.

 PubMed Web of Science ®Google Scholar

Binder M, Chmielarz P, Mckinnon PJ, Biggs LC, Thesleff I, Balic A. Functionally distinctive ptch receptors establish multimodal hedgehog signaling in the tooth epithelial stem cell niche. Stem Cells. 2019;37(9):1238–48. doi:10.1002/stem.3042.

 PubMed Web of Science ®Google Scholar

Zhang Y, Zhao X, Hu Y, St. Amand T, Zhang M, Ramamurthy R, Qiu M, Chen Y. Msx1 is required for the induction of patched by sonic hedgehog in the mammalian tooth germ. Dev Dyn. 1999;215(1):45–53. doi:10.1002/(SICI)1097-0177(199905)215:1<45::AID-DVDY5>3.0.CO;2-5.

 PubMed Web of Science ®Google Scholar

Hosoya A, Shalehin N, Takebe H, Shimo T, Irie K. Sonic hedgehog signaling and tooth development. Int J Mol Sci. 2020;21(5):1587. doi:10.3390/ijms21051587.

 PubMed Web of Science ®Google Scholar

Hardcastle Z, Mo R, Hui C, Sharpe PT. The shh signalling pathway in tooth development: defects in gli2 and gli3 mutants. Development. 1998;125(15):2803–11. doi:10.1242/dev.125.15.2803.

 PubMed Web of Science ®Google Scholar

Roh SY, Park J-C. The role of nuclear factor ic in tooth and bone development. J Korean Assoc Oral Maxillofac Surg. 2017;43(2):63–69. doi:10.5125/jkaoms.2017.43.2.63.

 PubMed Web of Science ®Google Scholar

Liu B, Chen S, Cheng D, Jing W, Helms J. Primary cilia integrate hedgehog and wnt signaling during tooth development. J Dent Res. 2014;93(5):475–82. doi:10.1177/0022034514528211.

 PubMed Web of Science ®Google Scholar

Ahn Y, Kim T, Choi H, Bae C, Yang Y, Baek J, Lee J, Cho E. Disruption of tgfbr2 in odontoblasts leads to aberrant pulp calcification. J Dent Res. 2015;94(6):828–35. doi:10.1177/0022034515577427.

 PubMed Web of Science ®Google Scholar

Wang X-P, Suomalainen M, Jorgez CJ, Matzuk MM, Werner S, Thesleff I. Follistatin regulates enamel patterning in mouse incisors by asymmetrically inhibiting bmp signaling and ameloblast differentiation. Dev Cell. 2004;7(5):719–30. doi:10.1016/j.devcel.2004.09.012.

 PubMed Web of Science ®Google Scholar

Heikinheimo K, Begue-Kirn C, Ritvos O, Tuuri T, Ruch J. The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro. J Dent Res. 1997;76(10):1625–36. doi:10.1177/00220345970760100301.

 PubMed Web of Science ®Google Scholar

Mitsiadis TA, Angeli I, James C, Lendahl U, Sharpe PT. Role of islet1 in the patterning of murine dentition. Development. 2003;130(18):4451–60. doi:10.1242/dev.00631.

 PubMed Web of Science ®Google Scholar

Laurikkala J, Kassai Y, Pakkasjärvi L, Thesleff I, Itoh N. Identification of a secreted bmp antagonist, ectodin, integrating bmp, fgf, and shh signals from the tooth enamel knot. Dev Biol. 2003;264(1):91–105. doi:10.1016/j.ydbio.2003.08.011.

 PubMed Web of Science ®Google Scholar

Yamashiro T, Tummers M, Thesleff I. Expression of bone morphogenetic proteins and msx genes during root formation. J Dent Res. 2003;82(3):172–76. doi:10.1177/154405910308200305.

 PubMed Web of Science ®Google Scholar

Åberg T, Wozney J, Thesleff I. Expression patterns of bone morphogenetic proteins (bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev Dyn. 1997;210(4):383–96. doi:10.1002/(SICI)1097-0177(199712)210:4<383::AID-AJA3>3.0.CO;2-C.

 PubMed Web of Science ®Google Scholar

Li X, Wang L, Su Q, Ye L, Zhou X, Zhang L, Song D, Huang D. Potential roles of bone morphogenetic protein 9 in the odontogenic differentiation of dental pulp cells. J Endod. 2021;47(3):436–43. doi:10.1016/j.joen.2020.10.018.

 PubMed Web of Science ®Google Scholar

Tao H, Li Q, Lin Y, Zuo H, Cui Y, Chen S, Chen Z, Liu H. Coordinated expression of p300 and hdac3 upregulates histone acetylation during dentinogenesis. J Cell Biochem. 2020;121(3):2478–88. doi:10.1002/jcb.29470.

 PubMed Web of Science ®Google Scholar

Mitsiadis TA, Catón J, Pagella P, Orsini G, Jimenez-Rojo L. Monitoring notch signaling-associated activation of stem cell niches within injured dental pulp. Front Physiol. 2017;8(372). doi:10.3389/fphys.2017.00372.

 Google Scholar

Peled A, Sarig O, Samuelov L, Bertolini M, Ziv L, Weissglas-Volkov D, Eskin-Schwartz M, Adase CA, Malchin N, Bochner R. Mutations in tspear, encoding a regulator of notch signaling, affect tooth and hair follicle morphogenesis. PLoS Genet. 2016;12(10):e1006369. doi:10.1371/journal.pgen.1006369.

 PubMed Web of Science ®Google Scholar

Qi S, Yan Y, Wen Y, Li J, Wang J, Chen F, Tang X, Shang G, Xu Y, Wang R. The effect of delta‐like 1 homologue on the proliferation and odontoblastic differentiation in human dental pulp stem cells. Cell Prolif. 2017;50(3):e12335. doi:10.1111/cpr.12335.

 PubMed Web of Science ®Google Scholar

Cluzeau C, Hadj‐Rabia S, Jambou M, Mansour S, Guigue P, Masmoudi S, Bal E, Chassaing N, Vincent MC, Viot G. Only four genes (eda1, edar, edaradd, and wnt10a) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011;32(1):70–72. doi:10.1002/humu.21384.

 PubMed Web of Science ®Google Scholar

Ohazama A, Courtney JM, Tucker AS, Naito A, Tanaka S, Inoue JI, Sharpe PT. Traf6 is essential for murine tooth cusp morphogenesis. Dev Dyn. 2004;229(1):131–35. doi:10.1002/dvdy.10400.

 PubMed Web of Science ®Google Scholar

Pispa J, Mikkola ML, Mustonen T, Thesleff I. Ectodysplasin, edar and tnfrsf19 are expressed in complementary and overlapping patterns during mouse embryogenesis. Gene Expression Patterns. 2003;3(5):675–79. doi:10.1016/S1567-133X(03)00092-9.

 PubMed Web of Science ®Google Scholar

Byers MR, Westenbroek RE. Odontoblasts in developing, mature and ageing rat teeth have multiple phenotypes that variably express all nine voltage-gated sodium channels. Arch Oral Biol. 2011;56(11):1199–220. doi:10.1016/j.archoralbio.2011.04.014.

 PubMed Web of Science ®Google Scholar

Yang J, Cai W, Lu X, Liu S, Zhao S. Rna-sequencing analyses demonstrate the involvement of canonical transient receptor potential channels in rat tooth germ development. Front Physiol. 2017;8(455). doi:10.3389/fphys.2017.00455.

 Google Scholar

Hou J, Situ Z, Duan X. Clc chloride channels in tooth germ and odontoblast-like mdpc-23 cells. Arch Oral Biol. 2008;53(9):874–78. doi:10.1016/j.archoralbio.2008.03.009.

 PubMed Web of Science ®Google Scholar

Kwon M, Baek SH, Park C-K, Chung G, Oh SB. Single-cell rt-pcr and immunocytochemical detection of mechanosensitive transient receptor potential channels in acutely isolated rat odontoblasts. Arch Oral Biol. 2014;59(12):1266–71. doi:10.1016/j.archoralbio.2014.07.016.

 PubMed Web of Science ®Google Scholar

Sato M, Ogura K, Kimura M, Nishi K, Ando M, Tazaki M, Shibukawa Y. Activation of mechanosensitive transient receptor potential/piezo channels in odontoblasts generates action potentials in cocultured isolectin b4–negative medium-sized trigeminal ganglion neurons. J Endod. 2018;44(6):984–991. e982. doi:10.1016/j.joen.2018.02.020.

 PubMed Web of Science ®Google Scholar

Lee K, Lee B-M, Park C-K, Kim YH, Chung G. Ion channels involved in tooth pain. Int J Mol Sci. 2019;20(9):2266. doi:10.3390/ijms20092266.

 PubMed Web of Science ®Google Scholar

Wang W, Yi X, Ren Y, Xie Q. Effects of adenosine triphosphate on proliferation and odontoblastic differentiation of human dental pulp cells. J Endod. 2016;42(10):1483–89. doi:10.1016/j.joen.2016.07.013.

 PubMed Web of Science ®Google Scholar

Felszeghy S, Módis L, Németh P, Nagy G, Zelles T, Agre P, Laurikkala J, Fejerskov O, Thesleff I, Nielsen S. Expression of aquaporin isoforms during human and mouse tooth development. Arch Oral Biol. 2004;49(4):247–57. doi:10.1016/j.archoralbio.2003.09.011.

 PubMed Web of Science ®Google Scholar

Gao Y, Sahlberg C, Kiukkonen A, Alaluusua S, Pohjanvirta R, Tuomisto J, Lukinmaa P-L. Lactational exposure of han/wistar rats to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin interferes with enamel maturation and retards dentin mineralization. J Dent Res. 2004;83(2):139–44. doi:10.1177/154405910408300211.

 PubMed Web of Science ®Google Scholar

Hur S-W, Oh S-H, Jeong B-C, Choi H, Kim J-W, Lee K-N, Hwang Y-C, Ryu J-H, Kim S-H, Koh J-T. Coup-tfii stimulates dentin sialophosphoprotein expression and mineralization in odontoblasts. J Dent Res. 2015;94(8):1135–42. doi:10.1177/0022034515585125.

 PubMed Web of Science ®Google Scholar

Gu J, Ikeda H, Suda H. Sympathetic regulation of tertiary dentinogenesis via beta-2 adrenergic receptor on rat odontoblasts. J Endod. 2015;41(7):1056–60. doi:10.1016/j.joen.2015.01.010.

 PubMed Web of Science ®Google Scholar

Wysolmerski JJ, Cormier S, Philbrick WM, Dann P, Zhang J-P, Roume J, Delezoide A-L, Silve C. Absence of functional type 1 parathyroid hormone (pth)/pth-related protein receptors in humans is associated with abnormal breast development and tooth impaction. J Clin Endocrinol Metab. 2001;86:1788–94.

 PubMed Web of Science ®Google Scholar

Matsumura S, Quispe-Salcedo A, Schiller C, Shin J, Locke B, Yakar S, Shimizu E. Igf-1 mediates ephrinb1 activation in regulating tertiary dentin formation. J Dent Res. 2017;96(10):1153–61. doi:10.1177/0022034517708572.

 PubMed Web of Science ®Google Scholar

Pääkkönen V, Saraniemi S, Bleicher F, Nevo Z, Tjäderhane L. Exostosin 1 is expressed in human odontoblasts. Arch Oral Biol. 2017;80:175–79. doi:10.1016/j.archoralbio.2017.04.004.

 PubMed Web of Science ®Google Scholar

Kato Y, Yokose S. Oxytocin facilitates dentinogenesis of rat dental pulp cells. J Endod. 2021;47(4):592–99. doi:10.1016/j.joen.2020.12.017.

 PubMed Web of Science ®Google Scholar

Ohshima H, Ajima H, Kawano Y, Nozawa-Inoue K, Wakisaka S, Maeda T. Transient expression of heat shock protein (hsp) 25 in the dental pulp and enamel organ during odontogenesis in the rat incisor. Arch Histol Cytol. 2000;63(4):381–95. doi:10.1679/aohc.63.381.

 PubMedGoogle Scholar

Chen T, Liu Z, Sun W, Li J, Liang Y, Yang X, Xu Y, Yu M, Tian W, Chen G. Inhibition of ape1 redox activity promotes odonto/osteogenic differentiation of dental papilla cells. Sci Rep. 2015;5(17483). doi:10.1038/srep17483.

 Google Scholar

Matsuishi YI, Kato H, Masuda K, Yamaza H, Hirofuji Y, Sato H, Wada H, Kiyoshima T, Nonaka K. Accelerated dentinogenesis by inhibiting the mitochondrial fission factor, dynamin related protein 1. Biochem Biophys Res Commun. 2018;495(2):1655–60. doi:10.1016/j.bbrc.2017.12.026.

 PubMed Web of Science ®Google Scholar

Couve E, Osorio R, Schmachtenberg O. Mitochondrial autophagy and lipofuscin accumulation in aging odontoblasts. J Dent Res. 2012;91(7):696–701. doi:10.1177/0022034512449347.

 PubMed Web of Science ®Google Scholar

Sehic A, Khuu C, Risnes S, Osmundsen H. Differential gene expression profiling of the molar tooth germ in peroxisome proliferator‐activated receptor‐α (ppar‐α) knockout mouse and in wild‐type mouse: molar tooth phenotype of ppar‐α knockout mouse. Eur J Oral Sci. 2009;117(2):93–104. doi:10.1111/j.1600-0722.2009.00615.x.

 PubMed Web of Science ®Google Scholar

Lee Y-H, Kang Y-M, Heo M-J, Kim G-E, Bhattarai G, Lee N-H, Yu M-K, Yi H-K. The survival role of peroxisome proliferator-activated receptor gamma induces odontoblast differentiation against oxidative stress in human dental pulp cells. J Endod. 2013;39(2):236–41. doi:10.1016/j.joen.2012.11.006.

 PubMed Web of Science ®Google Scholar

Chen H, Kang J, Zhang F, Yan T, Fan W, He H, Huang F. Sirt4 regulates rat dental papilla cell differentiation by promoting mitochondrial functions. Int J Biochem Cell Biol. 2021;134(105962):105962. doi:10.1016/j.biocel.2021.105962.

 PubMedGoogle Scholar

De Vicente J, Cabo R, Ciriaco E, Laura R, Naves F, Silos-Santiago I, Vega J. Impaired dental cytodifferentiation in glial cell-line derived growth factor (gdnf) deficient mice. Ann Anat-Anatomischer Anz. 2002;184(1):85–92. doi:10.1016/S0940-9602(02)80041-3.

 PubMed Web of Science ®Google Scholar

Nakatomi M, Quispe-Salcedo A, Sakaguchi M, Ida-Yonemochi H, Okano H, Ohshima H. Nestin expression is differently regulated between odontoblasts and the subodontoblastic layer in mice. Histochem Cell Biol. 2018;149(4):383–91. doi:10.1007/s00418-018-1651-3.

 PubMed Web of Science ®Google Scholar

Fried K, Risling M, Tidcombe H, Gassmann M, Lillesaar C. Expression of erbb3, erbb4, and neuregulin‐1 mrna during tooth development. Dev Dyn. 2002;224(3):356–60. doi:10.1002/dvdy.10114.

 PubMed Web of Science ®Google Scholar

Zhou C, Yang G, Chen M, Wang C, He L, Xiang L, Chen D, Ling J, Mao JJ. Lhx8 mediated wnt and tgfβ pathways in tooth development and regeneration. Biomaterials. 2015;3:35–46. doi:10.1016/j.biomaterials.2015.06.004.

 Google Scholar

Hoshino M, Hashimoto S, Muramatsu T, Matsuki M, Ogiuchi H, Shimono M. Claudin rather than occludin is essential for differentiation in rat incisor odontoblasts. Oral Dis. 2008;14(7):606–12. doi:10.1111/j.1601-0825.2007.01427.x.

 PubMed Web of Science ®Google Scholar

Palacios J, Benito N, Berraquero R, Pizarro A, Cano A, Gamallo C. Differential spatiotemporal expression of e-and p-cadherin during mouse tooth development. Int J Dev Biol. 2004;39:663–66.

 Google Scholar

Fried K, Mitsiadis T, Guerrier A, Haegerstrand A, Meister B. Combinatorial expression patterns of the connexins 26, 32, and 43 during development, homeostasis, and regeneration of rat teeth. Int J Dev Biol. 2003;40:985–95.

 Google Scholar

Yang J, Lu X, Liu S, Zhao S. The involvement of genes related to bile secretion pathway in rat tooth germ development. J Mol Histol. 2020;51(1):99–107. doi:10.1007/s10735-020-09861-0.

 PubMed Web of Science ®Google Scholar

Li G, Liu M, Zhang S, Wan H, Zhang Q, Yue R, Yan X, Wang X, Wang Z, Sun Y. Essential role of ift140 in promoting dentinogenesis. J Dent Res. 2018;97(4):423–31. doi:10.1177/0022034517741283.

 PubMed Web of Science ®Google Scholar

Wang X, Jong G, Lin LM, Shimizu E. Ephb–ephrinb interaction controls odontogenic/osteogenic differentiation with calcium hydroxide. J Endod. 2013;39(10):1256–60. doi:10.1016/j.joen.2013.06.016.

 PubMed Web of Science ®Google Scholar

Wang L, Yang H, Lin X, Cao Y, Gao P, Zheng Y, Fan Z. Kdm1a regulated the osteo/dentinogenic differentiation process of the stem cells of the apical papilla via binding with plod2. Cell Prolif. 2018;51(4):e12459. doi:10.1111/cpr.12459.

 PubMed Web of Science ®Google Scholar

Li QM, Li JL, Feng ZH, Lin HC, Xu Q. Effect of histone demethylase kdm5a on the odontogenic differentiation of human dental pulp cells. Bioengineered. 2020;11(1):449–62. doi:10.1080/21655979.2020.1743536.

 PubMed Web of Science ®Google Scholar

Schneider K, Korkmaz Y, Addicks K, Lang H, Raab WH-M. Prion protein (prp) in human teeth: an unprecedented pointer to prp’s function. J Endod. 2007;33(2):110–13. doi:10.1016/j.joen.2006.11.010.

 PubMed Web of Science ®Google Scholar

Li X-Y, Ban G-F, Al-Shameri B, He X, Liang D-Z, Chen W-X. High-temperature requirement protein a1 regulates odontoblastic differentiation of dental pulp cells via the transforming growth factor beta 1/smad signaling pathway. J Endod. 2018;44(5):765–72. doi:10.1016/j.joen.2018.02.003.

 PubMed Web of Science ®Google Scholar

Kim J-Y, Kim D-S, Auh Q-S, Yi J-K, Moon SU, Kim E-C. Role of protein phosphatase 1 in angiogenesis and odontoblastic differentiation of human dental pulp cells. J Endod. 2017;43(3):417–24. doi:10.1016/j.joen.2016.10.013.

 PubMed Web of Science ®Google Scholar

Yoshida S, Wada N, Hasegawa D, Miyaji H, Mitarai H, Tomokiyo A, Hamano S, Maeda H. Semaphorin 3a induces odontoblastic phenotype in dental pulp stem cells. J Dent Res. 2016;95(11):1282–90. doi:10.1177/0022034516653085.

 PubMed Web of Science ®Google Scholar

Park S, Lee Y, Lee D, Park J, Kim R, Shon W. Cpne7 induces biological dentin sealing in a dentin hypersensitivity model. J Dent Res. 2019;98(11):1239–44. doi:10.1177/0022034519869577.

 PubMed Web of Science ®Google Scholar

Maurin J-C, Couble M-L, Staquet M-J, Carrouel F, About I, Avila J, Magloire H, Bleicher F. Microtubule-associated protein 1b, a neuronal marker involved in odontoblast differentiation. J Endod. 2009;35(7):992–96. doi:10.1016/j.joen.2009.04.009.

 PubMed Web of Science ®Google Scholar

McKee M, Yadav M, Foster B, Somerman M, Farquharson C, Millán J. Compounded phospho1/alpl deficiencies reduce dentin mineralization. J Dent Res. 2013;92(8):721–27. doi:10.1177/0022034513490958.

 PubMed Web of Science ®Google Scholar

Park Y, Lee Y, Seo Y, Seo H, Park J, Bae H, Park J. Midkine promotes odontoblast-like differentiation and tertiary dentin formation. J Dent Res. 2020;0022034520925427.

 Web of Science ®Google Scholar

Zheng J, Nie X, He L, Yoon A, Wu L, Zhang X, Vats M, Schiff M, Xiang L, Tian Z. Epithelial cdc42 deletion induced enamel organ defects and cystogenesis. J Dent Res. 2018;97(12):1346–54. doi:10.1177/0022034518779546.

 PubMed Web of Science ®Google Scholar

Nakamura T, Unda F, De-Vega S, Vilaxa A, Fukumoto S, Yamada KM, Yamada Y. The krüppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation. J Biol Chem. 2004;279(1):626–34. doi:10.1074/jbc.M307502200.

 PubMed Web of Science ®Google Scholar

Bouwman P, Göllner H, Elsässer HP, Eckhoff G, Karis A, Grosveld F, Philipsen S, Suske G. Transcription factor sp3 is essential for post‐natal survival and late tooth development. EMBO J. 2000;19(4):655–61. doi:10.1093/emboj/19.4.655.

 PubMed Web of Science ®Google Scholar

Jimenez-Rojo L, Ibarretxe G, Aurrekoetxea M, de Vega S, Nakamura T, Yamada Y, Unda F. Epiprofin-sp6. A new player in the regulation of tooth development. Histol Histopathol. 2010;25(12):1621–30. doi:10.14670/HH-25.1621.

 PubMed Web of Science ®Google Scholar

Bae JM, Clarke JC, Rashid H, Adhami MD, McCullough K, Scott JS, Chen H, Sinha KM, de Crombrugghe B, Javed A. Specificity protein 7 is required for proliferation and differentiation of ameloblasts and odontoblasts. J Bone Miner Res. 2018;33(6):1126–40. doi:10.1002/jbmr.3401.

 PubMed Web of Science ®Google Scholar

Xiao Y, Lin YX, Cui Y, Zhang Q, Pei F, Zuo HY, Liu H, Chen Z. Zeb1 promotes odontoblast differentiation in a stage-dependent manner. J Dent Res. 2021;22034520982249.

 Web of Science ®Google Scholar

Aryal YP, Neupane S, Kim TY, Lee ES, Pokhrel NK, Yeon CY, Kim JY, An CH, An SY, Park EK, et al. Developmental roles of fuse binding protein 1 (fubp1) in tooth morphogenesis. Int J Mol Sci. 2020;21(21):8079. doi:10.3390/ijms21218079.

 PubMed Web of Science ®Google Scholar

Zhang Y, Fang M, Yang Z, Qin W, Guo S, Ma J, Chen W. Gata binding protein 4 regulates tooth root dentin development via fbp1. Int J Biol Sci. 2020;16(1):181–93. doi:10.7150/ijbs.36567.

 PubMed Web of Science ®Google Scholar

De Coster P, Cornelissen M, De Paepe A, Martens L, Vral A. Abnormal dentin structure in two novel gene mutations [col1a1, arg134cys] and [adamts2, trp795-to-ter] causing rare type i collagen disorders. Arch Oral Biol. 2007;52(2):101–09. doi:10.1016/j.archoralbio.2006.08.007.

 PubMed Web of Science ®Google Scholar

Goss M, Socorro M, Monier D, Verdelis K, Napierala D. Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells. Mol Genet Metab. 2019;126(4):504–12. doi:10.1016/j.ymgme.2019.01.014.

 PubMed Web of Science ®Google Scholar

Abe M, Tamamura Y, Yamagishi H, Maeda T, Kato J, Tabata MJ, Srivastava D, Wakisaka S, Kurisu K. Tooth-type specific expression of dhand/hand2: possible involvement in murine lower incisor morphogenesis. Cell Tissue Res. 2002;310(2):201–12. doi:10.1007/s00441-002-0611-2.

 PubMed Web of Science ®Google Scholar

Zhang Y, Lian M, Zhao X, Cao P, Xiao J, Shen S, Tang W, Zhang J, Hao J, Feng X. Rick regulates the odontogenic differentiation of dental pulp stem cells through activation of tnf-alpha via the erk and not through nf-kappab signaling pathway. Cell Biol Int. 2020.

 Web of Science ®Google Scholar

Fu J, Zheng H, Xue Y, Jin R, Yang G, Chen Z, Yuan G. Wwp2 promotes odontoblastic differentiation by monoubiquitinating klf5. J Dent Res. 2020;22034520970866.

 Web of Science ®Google Scholar

Lekszas C, Foresti O, Raote I, Liedtke D, Konig EM, Nanda I, Vona B, De Coster P, Cauwels R, Malhotra V, et al. Biallelic tango1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion. Elife. 2020;9. doi:10.7554/eLife.51319.

 PubMed Web of Science ®Google Scholar

Tohma A, Ohkura N, Yoshiba K, Takeuchi R, Yoshiba N, Edanami N, Shirakashi M, Ibn Belal RS, Ohshima H, Noiri Y. Glucose transporter 2 and 4 are involved in glucose supply during pulpal wound healing after pulpotomy with mineral trioxide aggregate in rat molars. J Endod. 2020;46(1):81–88. doi:10.1016/j.joen.2019.10.003.

 PubMed Web of Science ®Google Scholar

Yan W, Cao Y, Yang H, Han N, Zhu X, Fan Z, Du J, Zhang F. Cb1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 mapk and jnk in an inflammatory environment. Cell Prolif. 2019;52(6):e12691. doi:10.1111/cpr.12691.

 PubMed Web of Science ®Google Scholar

Fujihara H, Nozaki T, Tsutsumi M, Isumi M, Shimoda S, Hamada Y, Masutani M. Spontaneous development of dental dysplasia in aged parp-1 knockout mice. Cells. 2019;8(10). doi:10.3390/cells8101157.

 PubMed Web of Science ®Google Scholar

Jiang S, Sheng R, Qi X, Wang J, Guo Y, Yuan Q. Usp34 regulates tooth root morphogenesis by stabilizing nfic. Int J Oral Sci. 2021;13(1):7. doi:10.1038/s41368-021-00114-8.

 PubMed Web of Science ®Google Scholar

Luo X, Yin J, Miao S, Feng W, Ning T, Xu S, Huang S, Zhang S, Liao Y, Hao C, et al. Mtorc1 promotes mineralization via p53 pathway. FASEB J. 2021;35(2):e21325. doi:10.1096/fj.202002016R.

 PubMed Web of Science ®Google Scholar