Role of connexin 43 in odontoblastic differentiation and structural maintenance in pulp damage repair

Jiaxin Yin , Jue Xu , Ran Cheng , Meiying Shao , Yuandong Qin , Hui Yang , Tao Hu

International Journal of Oral Science ›› 2021, Vol. 13 ›› Issue (1) : 1

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International Journal of Oral Science ›› 2021, Vol. 13 ›› Issue (1) : 1 DOI: 10.1038/s41368-020-00105-1
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Role of connexin 43 in odontoblastic differentiation and structural maintenance in pulp damage repair

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Abstract

Dental pulp can initiate its damage repair after an injury of the pulp–dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp–dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.

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Jiaxin Yin, Jue Xu, Ran Cheng, Meiying Shao, Yuandong Qin, Hui Yang, Tao Hu. Role of connexin 43 in odontoblastic differentiation and structural maintenance in pulp damage repair. International Journal of Oral Science, 2021, 13(1): 1 DOI:10.1038/s41368-020-00105-1

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References

[1]

Smith AJ, . Reactionary dentinogenesis. Int. J. Dev. Biol., 1995, 39: 273-280.

[2]

Charadram N, . Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix. Bone, 2012, 50: 265-275.

[3]

Lesot H, Begue-Kim C, Kubler MD, Meyer JM. Experimental induction of odontoblast differentiation and stimulation during reparative processes. Cells Mater., 1993, 3: 201-217.

[4]

Gronthos S, . Stem cell properties of human dental pulp stem cells. J. Dent. Res., 2002, 81: 531-535.

[5]

Hu L, Liu Y, Wang S. Stem cell-based tooth and periodontal regeneration. Oral. Dis., 2018, 24: 696-705.

[6]

Dammaschke T. The formation of reparative dentine and Höhl cells in the dental pulp. ENDO, 2010, 4: 255-261.

[7]

Yianni V, Sharpe PT. Molecular programming of perivascular stem cell precursors. Stem Cells, 2018, 36: 1890-1904.

[8]

Vidovic-Zdrilic I, . FGF2 enhances odontoblast differentiation by αSMA+ progenitors in vivo. J. Dent. Res., 2018, 97: 1170-1177.

[9]

Zhao X, . Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells. Mol. Biol. Rep., 2012, 39: 215-220.

[10]

Goldberg M, Smith AJ. Cells and extracellular matrices of dentin and pulp: a biological basis for repair and tissue engineering. Crit. Rev. Oral. Biol. Med., 2004, 15: 13-27.

[11]

Zheng Y, . Dentin regeneration using deciduous pulp stem/progenitor cells. J. Dent. Res., 2012, 91: 676-682.

[12]

Nowicka A, . Response of human dental pulp capped with biodentine and mineral trioxide aggregate. J. Endod., 2013, 39: 743-747.

[13]

Tziafa C, Koliniotou-Koumpia E, Papadimitriou S, Tziafas D. Dentinogenic responses after direct pulp capping of miniature swine teeth with biodentine. J. Endod., 2014, 40: 1967-1971.

[14]

Ruch JV. Odontoblast commitment and differentiation. Biochem. Cell Biol., 1998, 76: 923-938.

[15]

Ruch JV, Lesot H, Bègue-Kirn C. Odontoblast differentiation. Int. J. Dev. Biol., 1995, 39: 51-68.

[16]

Linde A, Goldberg M. Dentinogenesis. Crit. Rev. Oral. Biol. Med., 1993, 4: 679-728.

[17]

Mazel T. Crosstalk of cell polarity signaling pathways. Protoplasma, 2017, 254: 1241-1258.

[18]

Chang B, Svoboda KKH, Liu X. Cell polarization: from epithelial cells to odontoblasts. Eur. J. Cell Biol., 2019, 98: 1-11.

[19]

Kelly JJ, Simek J, Laird DW. Mechanisms linking connexin mutations to human diseases. Cell Tissue Res., 2015, 360: 701-721.

[20]

Ke Q, . Connexin43 is involved in the generation of human-induced pluripotent stem cells. Hum. Mol. Genet., 2013, 22: 2221-2233.

[21]

Ma L, . Connexin43 hemichannels protect bone loss during estrogen deficiency. Bone Res., 2019, 22: 11.

[22]

Solan JL, Lampe PD. Connexin43 phosphorylation: structural changes and biological effects. Biochem. J., 2009, 419: 261-272.

[23]

Márquez-Rosado L, Solan JL, Dunn CA, Norris RP, Lampe PD. Connexin43 phosphorylation in brain, cardiac, endothelial and epithelial tissues. Biochim. Biophys. Acta, 2012, 1818: 1985-1992.

[24]

Bazzoun D, . Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium. J. Cell Sci., 2019, 132: jcs223313.

[25]

Pace NP, . Two novel GJA1 variants in oculodentodigital dysplasia. Mol. Genet. Genom. Med., 2019, 7

[26]

Hashida Y, . Communication-dependent mineralization of osteoblasts via gap junctions. Bone, 2014, 61: 19-26.

[27]

Misu A, . Two different functions of connexin43 confer two different bone phenotypes in Zebrafish. J. Biol. Chem., 2016, 291: 12601-12611.

[28]

Li S, . Connexin43-containing gap junctions potentiate extracellular Ca2+-induced odontoblastic differentiation of human dental pulp stem cells via Erk1/2. Exp. Cell Res., 2015, 338: 1-9.

[29]

Neves VCM, Sharpe PT. Regulation of reactionary dentine formation. J. Dent. Res., 2018, 97: 416-422.

[30]

Sagomonyants K, Kalajzic I, Maye P, Mina M. FGF signaling prevents the terminal differentiation of odontoblasts. J. Dent. Res., 2017, 96: 663-670.

[31]

Tziafas D. Characterization of odontoblast-like cell phenotype and reparative dentin formation in vivo: a comprehensive literature review. J. Endod., 2019, 45: 241-249.

[32]

Tziafa C, Koliniotou-Koumpia E, Papadimitriou S, Tziafas D. Dentinogenic activity of biodentine in deep cavities of miniature swine teeth. J. Endod., 2015, 41: 1161-1166.

[33]

Six N, Lasfargues JJ, Goldberg M. Differential repair responses in the coronal and radicular areas of the exposed rat molar pulp induced by recombinant human bone morphogenetic protein 7 (osteogenic protein 1). Arch. Oral. Biol., 2002, 47: 177-187.

[34]

Goldberg M, Njeh A, Uzunoglu E. Is pulp inflammation a prerequisite for pulp healing and regeneration?. Mediators Inflamm., 2015, 2015: 347649.

[35]

Kawashima N, Okiji T. Odontoblasts: specialized hard-tissue-forming cells in the dentin-pulp complex. Congenit. Anom. (Kyoto)., 2016, 56: 144-153.

[36]

Li Q, . FAM20C could be targeted by TET1 to promote odontoblastic differentiation potential of human DPCs. Cell Prolif., 2018, 51

[37]

Wei X, Ling J, Wu L, Liu L, Xiao Y. Expression of mineralization markers in dental pulp cells. J. Endod., 2007, 33: 703-708.

[38]

Shao MY, . The presence of open dentinal tubules affects the biological properties of dental pulp cells ex vivo. Mol. Cells, 2011, 31: 65-71.

[39]

Bleicher F. Odontoblast physiology. Exp. Cell Res., 2014, 325: 65-71.

[40]

Martins-Marques T, . Biological functions of connexin43 beyond intercellular communication. Trends Cell Biol., 2019, 29: 835-847.

[41]

Couve E, Osorio R, Schmachtenberg O. Reactionary dentinogenesis and neuroimmune response in dental caries. J. Dent. Res., 2014, 93: 788-793.

[42]

Farahani RM, Nguyen KA, Simonian M, Hunter N. Adaptive calcified matrix response of dental pulp to bacterial invasion is associated with establishment of a network of glial fibrillary acidic protein+/glutamine synthetase+ cells. Am. J. Pathol., 2010, 177: 1901-1914.

[43]

Muramatsu T, . Reduction of connexin43 expression in aged human dental pulp. Int. Endod. J., 2004, 37: 814-818.

[44]

Hur KC, Shim JE, Johnson RG. A potential role forcx43-hemichannels in staurosporin-induced apoptosis. Cell Commun. Adhes., 2003, 10: 271-277.

[45]

Fukuda S, Akiyama M, Harada H, Nakahama KI. Effect of gap junction-mediated intercellular communication on TGF-β induced epithelial-to-mesenchymal transition. Biochem. Biophys. Res. Commun., 2019, 508: 928-933.

[46]

Lagos-Cabré R, . Intracellular Ca2+ increases and connexin 43 hemichannel opening are necessary but not sufficient for Thy-1-induced astrocyte migration. Int. J. Mol. Sci., 2018, 19: 2179.

[47]

Giepmans BN, van Ijzendoorn SC. Epithelial cell-cell junctions and plasma membrane domains. Biochim. Biophys. Acta, 2009, 1788: 820-831.

[48]

Couve E, Osorio R, Schmachtenberg O. The amazing odontoblast: activity, autophagy, and aging. J. Dent. Res., 2013, 92: 765-772.

[49]

Ritchie H. The functional significance of dentin sialoprotein-phosphophoryn and dentin sialoprotein. Int. J. Oral. Sci., 2018, 10: 31.

[50]

Rao LJ, Yi BC, Li QM, Xu Q. TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells. Int. J. Oral. Sci., 2016, 8: 110-116.

[51]

About I, Proust JP, Raffo S, Mitsiadis TA, Franquin JC. In vivo and in vitro expression of connexin43 in human teeth. Connect. Tissue Res., 2002, 43: 232-237.

[52]

Chung CK, Muramatsu T, Uekusa T, Sasaki H, Shimono M. Inhibition of connexin43 expression and function in cultured rat dental pulp cells by antisense oligonucleotide. Cell Tissue Res., 2007, 329: 295-300.

[53]

Iohara K, . Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J. Dent. Res., 2004, 83: 590-595.

[54]

Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl Acad. Sci. USA, 2000, 97: 13625-13630.

[55]

Cheng R, . Roles of lysophosphatidic acid and the Rho-associated kinase pathway in the migration of dental pulp cells. Exp. Cell Res., 2010, 316: 1019-1027.

[56]

Cheng R, . The effect of lysophosphatidic acid and Rho associated kinase patterning on adhesion of dental pulp cells. Int. Endod. J., 2011, 44: 2-8.

Funding

the Sichuan Provincial Natural Science Foundation of China (grant number: 2018SZ0139) Fundamental Research Funds for the Central Universities (grant number: 2018SCU12013)

National Natural Science Foundation of China (National Science Foundation of China)(81500846)

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