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Erschienen in: Clinical Oral Investigations 3/2021

04.07.2020 | Original Article

Pulpal upregulation of connexin 43 during pulpitis

verfasst von: Wen Yi Lim, Leigh Edward Madden, David Laurence Becker

Erschienen in: Clinical Oral Investigations | Ausgabe 3/2021

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Abstract

Objectives

Connexins are building blocks of membranous channels that form gap junctions and hemichannels. These channels are essential portals for information exchange and coordination during inflammation. Pathologic levels of these conduits may result in excessive inflammation and collateral destruction. This study aimed to analyse temporospatial levels of connexin 43 (Cx43) during pulpitis in extracted human teeth and in a rodent model. A specific interest was directed at the pulpal stroma as it is conserved during vital pulp therapy.

Materials and methods

Pulpal tissues were attained from human extracted teeth of various pulpal inflammatory stages and fixed for cryosections. Pulpal exposures were created in bilateral maxillary molars in Sprague-Dawley rats. Rats were sacrificed at days 1 to 5 post-exposure. Immunofluorescence histology was performed to detect Cx43, markers for inflammation, and cell death. Immunofluorescent levels in the pulpal stroma at 3 sites (wound/near/far) were matched to pulpal condition (human) or days post-exposure (rodent).

Results

Cx43 upregulation was observed with increased severity of pulpitis both in humans and rodent model. The upregulation appeared to be global and included distant regions. Elevated levels of neutrophils were present in advanced pulpitis. Apoptosis and necroptosis seem to be upregulated in human samples as Cx43 levels rose.

Conclusions

We observed a disseminated upregulation of Cx43 throughout the pulpal stroma as inflammation became advanced. This observation may facilitate cell death signal transfer or represent overt levels of purinergic signalling that leads to pro-inflammatory conditions.

Clinical relevance

Cx43 downregulation may represent a potential therapeutic approach to enable resolution of pulpal inflammation.
Literatur
1.
Zurück zum Zitat Bjørndal L, Reit C, Bruun G et al (2010) Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy. Eur J Oral Sci 118(3):290–297CrossRef Bjørndal L, Reit C, Bruun G et al (2010) Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy. Eur J Oral Sci 118(3):290–297CrossRef
2.
Zurück zum Zitat Taha NA, Abdelkhader SZ (2018) Outcome of full pulpotomy using biodentine in adult patients with symptoms indicative of irreversible pulpitis. Int Endod J 46(3):383–390 Taha NA, Abdelkhader SZ (2018) Outcome of full pulpotomy using biodentine in adult patients with symptoms indicative of irreversible pulpitis. Int Endod J 46(3):383–390
3.
Zurück zum Zitat Tan SY, Yu VSH, Lim KC, Tan BCK, Neo CLJ, Shen L, Messer HH (2020) Long-term pulpal and restorative outcomes of pulpotomy in mature permanent teeth. J Endod 46(3):383–390CrossRef Tan SY, Yu VSH, Lim KC, Tan BCK, Neo CLJ, Shen L, Messer HH (2020) Long-term pulpal and restorative outcomes of pulpotomy in mature permanent teeth. J Endod 46(3):383–390CrossRef
4.
Zurück zum Zitat Goodenough Daniel A, Goliger JA, Paul DL (1996) Connexins, connexons, and intercellular communication. Annu Rev Biochem 65:475–502CrossRef Goodenough Daniel A, Goliger JA, Paul DL (1996) Connexins, connexons, and intercellular communication. Annu Rev Biochem 65:475–502CrossRef
5.
Zurück zum Zitat Becker DL, Phillips AR, Duft BJ, Kim Y, Green CR (2016) Translating connexin biology into therapeutics. Semin Cell Dev Biol 50:49–58CrossRef Becker DL, Phillips AR, Duft BJ, Kim Y, Green CR (2016) Translating connexin biology into therapeutics. Semin Cell Dev Biol 50:49–58CrossRef
6.
Zurück zum Zitat Beyer EC, Paul DL, Goodenough DA (1987) Connexin43: a protein from rat heart homologous to a gap junction protein from liver. J Cell Biol 105(6 I):2621–2629CrossRef Beyer EC, Paul DL, Goodenough DA (1987) Connexin43: a protein from rat heart homologous to a gap junction protein from liver. J Cell Biol 105(6 I):2621–2629CrossRef
7.
Zurück zum Zitat Sáez JC, Retamal MA, Basilio D et al (1711) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta - Biomembr 2005:215–224 Sáez JC, Retamal MA, Basilio D et al (1711) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta - Biomembr 2005:215–224
8.
Zurück zum Zitat Decrock E, De Vuyst E, Vinken M et al (2009) Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. Cell Death Differ 16(1):151–163CrossRef Decrock E, De Vuyst E, Vinken M et al (2009) Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. Cell Death Differ 16(1):151–163CrossRef
9.
Zurück zum Zitat Ebihara L (2003) New roles for connexons. News Physiol Sci 18:100–103PubMed Ebihara L (2003) New roles for connexons. News Physiol Sci 18:100–103PubMed
10.
Zurück zum Zitat Quist AP, Rhee SK, Lin H, Lal R (2000) Physiological role of gap-junctional hemichannels: extracellular calcium-dependent isosmotic volume regulation. J Cell Biol 148:1063–1074CrossRef Quist AP, Rhee SK, Lin H, Lal R (2000) Physiological role of gap-junctional hemichannels: extracellular calcium-dependent isosmotic volume regulation. J Cell Biol 148:1063–1074CrossRef
11.
Zurück zum Zitat Freeman SM (1993) Abboud Camille, Freeman Scott M., et al. The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 53:5274–5283PubMed Freeman SM (1993) Abboud Camille, Freeman Scott M., et al. The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 53:5274–5283PubMed
12.
Zurück zum Zitat Lin Jane HC, Weigel H, Cotrina ML et al (199) Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci 81(8):494–500 Lin Jane HC, Weigel H, Cotrina ML et al (199) Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci 81(8):494–500
13.
Zurück zum Zitat Fried KAJ, Mitsiadis TA, Guerrier A, Haegerstrand A, Meister B (1996) Combinatorial expression patterns of the connexins and regeneration of rat teeth. Int J Dev Biol 995:985–995 Fried KAJ, Mitsiadis TA, Guerrier A, Haegerstrand A, Meister B (1996) Combinatorial expression patterns of the connexins and regeneration of rat teeth. Int J Dev Biol 995:985–995
14.
Zurück zum Zitat About I, Proust JP, Raffo S et al (2002) In vivo and in vitro expression of connexin 43 in human teeth. Connect Tissue Res 43(2–3):232–237CrossRef About I, Proust JP, Raffo S et al (2002) In vivo and in vitro expression of connexin 43 in human teeth. Connect Tissue Res 43(2–3):232–237CrossRef
15.
Zurück zum Zitat Farahani RM, Nguyen KA, Simonian M, Hunter N (2010) 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 177(4):1901–1914CrossRef Farahani RM, Nguyen KA, Simonian M, Hunter N (2010) 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 177(4):1901–1914CrossRef
16.
Zurück zum Zitat Couve E, Osorio R, Schmachtenberg O (2014) Reactionary dentinogenesis and neuroimmune response in dental caries. J Dent Res 93(8):788–793CrossRef Couve E, Osorio R, Schmachtenberg O (2014) Reactionary dentinogenesis and neuroimmune response in dental caries. J Dent Res 93(8):788–793CrossRef
17.
Zurück zum Zitat Ikeda H, Suda H (2013) Odontoblastic syncytium through electrical coupling in the human dental pulp. J Dent Res 92(4):371–375CrossRef Ikeda H, Suda H (2013) Odontoblastic syncytium through electrical coupling in the human dental pulp. J Dent Res 92(4):371–375CrossRef
18.
Zurück zum Zitat Li S, He H, Zhang G, Wang F, Zhang P, Tan Y (2015) Connexin43-containing gap junctions potentiate extracellular Ca2+−induced odontoblastic differentiation of human dental pulp stem cells via Erk1/2. Exp Cell Res 338(1):1–9CrossRef Li S, He H, Zhang G, Wang F, Zhang P, Tan Y (2015) Connexin43-containing gap junctions potentiate extracellular Ca2+−induced odontoblastic differentiation of human dental pulp stem cells via Erk1/2. Exp Cell Res 338(1):1–9CrossRef
19.
Zurück zum Zitat Murakami S, Muramatsu T, Shimono M (2001) Expression and localization of connexin 43 in rat incisor odontoblasts. Anat Embryol (Berl) 203(5):367–374CrossRef Murakami S, Muramatsu T, Shimono M (2001) Expression and localization of connexin 43 in rat incisor odontoblasts. Anat Embryol (Berl) 203(5):367–374CrossRef
20.
Zurück zum Zitat Krysko DV, Leybaert L, Vandenabeele P, D’Herde K (2005) Gap junctions and the propagation of cell survival and cell death signals. Apoptosis 10(3):459–469CrossRef Krysko DV, Leybaert L, Vandenabeele P, D’Herde K (2005) Gap junctions and the propagation of cell survival and cell death signals. Apoptosis 10(3):459–469CrossRef
21.
Zurück zum Zitat Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565CrossRef Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565CrossRef
22.
Zurück zum Zitat Garcia-Dorado D, Inserte J, Ruiz-Meana M et al (1997) Gap junction uncoupler heptanol prevents cell-to-cell progression of hypercontracture and limits necrosis during myocardial reperfusion. Circulation 96(10):3579–3586CrossRef Garcia-Dorado D, Inserte J, Ruiz-Meana M et al (1997) Gap junction uncoupler heptanol prevents cell-to-cell progression of hypercontracture and limits necrosis during myocardial reperfusion. Circulation 96(10):3579–3586CrossRef
23.
Zurück zum Zitat García-Dorado D, Rodríguez-Sinovas A, Ruiz-Meana M (2004) Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion. Cardiovasc Res 61(3):386–401CrossRef García-Dorado D, Rodríguez-Sinovas A, Ruiz-Meana M (2004) Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion. Cardiovasc Res 61(3):386–401CrossRef
24.
Zurück zum Zitat Duffy HS, John GR, Lee SC et al (2000) Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes. J Neurosci 20(RC114):1–6 Duffy HS, John GR, Lee SC et al (2000) Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes. J Neurosci 20(RC114):1–6
25.
Zurück zum Zitat De Vuyst E, Decrock E, De Bock M et al (2007) Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor. Mol Biol Cell 18:34–46CrossRef De Vuyst E, Decrock E, De Bock M et al (2007) Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor. Mol Biol Cell 18:34–46CrossRef
26.
Zurück zum Zitat Srinivas M, Calderon DP, Kronengold J, Verselis VK (2006) Regulation of connexin hemichannels by monovalent cations. J Gen Physiol 27:67–75CrossRef Srinivas M, Calderon DP, Kronengold J, Verselis VK (2006) Regulation of connexin hemichannels by monovalent cations. J Gen Physiol 27:67–75CrossRef
27.
Zurück zum Zitat Riquelme MA, Jiang JX (2013) Elevated intracellular Ca2+ signals by oxidative stress activate connexin 43 hemichannels in osteocytes. Bone Res 1:355–361CrossRef Riquelme MA, Jiang JX (2013) Elevated intracellular Ca2+ signals by oxidative stress activate connexin 43 hemichannels in osteocytes. Bone Res 1:355–361CrossRef
28.
Zurück zum Zitat Calder BW, Matthew RJ, Bainbridge H et al (2015) Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early Inflammation during the foreign body response. Tissue Eng - Part A 21:1752–1762CrossRef Calder BW, Matthew RJ, Bainbridge H et al (2015) Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early Inflammation during the foreign body response. Tissue Eng - Part A 21:1752–1762CrossRef
29.
Zurück zum Zitat Kim Y, Davidson JO, Gunn KC, Phillips AR et al (2016) Role of hemichannels in CNS inflammation and the inflammasome pathway. In: Rossen D (ed) Advances in Protein Chemistry and Structural Biology, vol 104. Academic Press Inc., San Diego, pp 1–37 Kim Y, Davidson JO, Gunn KC, Phillips AR et al (2016) Role of hemichannels in CNS inflammation and the inflammasome pathway. In: Rossen D (ed) Advances in Protein Chemistry and Structural Biology, vol 104. Academic Press Inc., San Diego, pp 1–37
30.
Zurück zum Zitat Chanson M, Derouette JP, Roth I et al (1711) Gap junctional communication in tissue inflammation and repair. Biochim Biophys Acta - Biomembr 2005:197–207 Chanson M, Derouette JP, Roth I et al (1711) Gap junctional communication in tissue inflammation and repair. Biochim Biophys Acta - Biomembr 2005:197–207
31.
Zurück zum Zitat Li W, Bao G, Chen W et al (2018) Connexin 43 hemichannel as a novel mediator of sterile and infectious inflammatory diseases. Sci Rep 8(1):1–5CrossRef Li W, Bao G, Chen W et al (2018) Connexin 43 hemichannel as a novel mediator of sterile and infectious inflammatory diseases. Sci Rep 8(1):1–5CrossRef
32.
Zurück zum Zitat Frank D, Vince JE (2019) Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 26:99–114CrossRef Frank D, Vince JE (2019) Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 26:99–114CrossRef
Metadaten
Titel
Pulpal upregulation of connexin 43 during pulpitis
verfasst von
Wen Yi Lim
Leigh Edward Madden
David Laurence Becker
Publikationsdatum
04.07.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 3/2021
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-020-03439-6

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