Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Oral Investigations
Published in: Clinical Oral Investigations 3/2021

01-03-2021 | Original Article

Pulpal upregulation of connexin 43 during pulpitis

Authors: Wen Yi Lim, Leigh Edward Madden, David Laurence Becker

Published in: Clinical Oral Investigations | Issue 3/2021

Login to get access

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.
Literature
1.
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.
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.
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.
Goodenough Daniel A, Goliger JA, Paul DL (1996) Connexins, connexons, and intercellular communication. Annu Rev Biochem 65:475–502CrossRef
5.
Becker DL, Phillips AR, Duft BJ, Kim Y, Green CR (2016) Translating connexin biology into therapeutics. Semin Cell Dev Biol 50:49–58CrossRef
6.
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.
Sáez JC, Retamal MA, Basilio D et al (1711) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta - Biomembr 2005:215–224
8.
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.
Ebihara L (2003) New roles for connexons. News Physiol Sci 18:100–103PubMed
10.
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.
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.
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.
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.
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.
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.
Couve E, Osorio R, Schmachtenberg O (2014) Reactionary dentinogenesis and neuroimmune response in dental caries. J Dent Res 93(8):788–793CrossRef
17.
Ikeda H, Suda H (2013) Odontoblastic syncytium through electrical coupling in the human dental pulp. J Dent Res 92(4):371–375CrossRef
18.
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.
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.
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.
Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565CrossRef
22.
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.
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.
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.
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.
Srinivas M, Calderon DP, Kronengold J, Verselis VK (2006) Regulation of connexin hemichannels by monovalent cations. J Gen Physiol 27:67–75CrossRef
27.
Riquelme MA, Jiang JX (2013) Elevated intracellular Ca2+ signals by oxidative stress activate connexin 43 hemichannels in osteocytes. Bone Res 1:355–361CrossRef
28.
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.
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.
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.
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.
Frank D, Vince JE (2019) Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 26:99–114CrossRef
Metadata
Title
Pulpal upregulation of connexin 43 during pulpitis
Authors
Wen Yi Lim
Leigh Edward Madden
David Laurence Becker
Publication date
01-03-2021
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 3/2021
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-020-03439-6

Other articles of this Issue 3/2021

Clinical Oral Investigations 3/2021 Go to the issue

Original Article

Subgingival microflora in adolescent females with polycystic ovary syndrome and its association with oral hygiene, gingivitis, and selected metabolic and hormonal parameters

Original Article

Efficacy of Er,Cr:YSGG laser–assisted delivery of topical anesthesia in the oral mucosa

Original Article

Accuracy of fully guided orthodontic mini-implant placement evaluated by cone-beam computed tomography: a study involving human cadaver heads

Original Article

The effect of lipoxin A4 on E. coli LPS-induced osteoclastogenesis

Original Article

A retrospective analysis of dental implantation under anticoagulant treatment

Original Article

Machine learning in prediction of genetic risk of nonsyndromic oral clefts in the Brazilian population