Expression of Pannexin3 in human odontoblast-like cells and its hemichannel function in mediating ATP release

Fu, Donglei; Song, Frank M.; Sun, Hairong; Pei, Dandan; Wang, Yake; Lei, Jian; Huang, Cui

doi:10.1016/j.archoralbio.2015.07.005

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…Immunofluorescence results showed that Panx3 was expressed in the cell membrane and cytoplasm (Fig. 2C), which was consistent with previous study that Panx3 is expressed in plasma membrane and diffusely in the cytosol acting as and ER Ca 2+ channel [19,21].…”

Section: Tnf-a Concentration Dependency Of Panx3 Expression In Hdpcssupporting

confidence: 92%

“…Panx3, the third member of Panxs family, is involved in the regulation of dynamic biological functions and plays a critical role in pathogenesis of many diseases [22], such as saturated fatty acid-induced inflammation [16], osteoarthritis [23] and dentin hypersensitivity [19]. However, the effect of Panx3 in defined cell populations on pulpitis remains unascertained.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the hemichannel function, Panx3 participates in several intracellular signalling pathways, and regulates gene expression and cell activity 17, 18. In addition, our previous study has demonstrated that Panx3 was expressed in human dental pulp tissues and human odontoblastic‐like cells 19. These inspire us to hypothesize that single Panx3 plays critical roles during dental pulp inflammation.…”

Section: Introductionmentioning

confidence: 98%

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Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

Song

Sun

Wang

et al. 2016

J Cellular Molecular Medi

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Human dental pulp cells (HDPCs) play a crucial role in dental pulp inflammation. Pannexin 3 (Panx3), a member of Panxs (Pannexins), has been recently found to be involved in inflammation. However, the mechanism of Panx3 in human dental pulp inflammation remains unclear. In this study, the role of Panx3 in inflammatory response was firstly explored, and its potential mechanism was proposed. Immunohistochemical staining showed that Panx3 levels were diminished in inflamed human and rat dental pulp tissues. In vitro, Panx3 expression was significantly down‐regulated in HDPCs following a TNF‐α challenge in a concentration‐dependent way, which reached the lowest level at 10 ng/ml of TNF‐α. Such decrease could be reversed by MG132, a proteasome inhibitor. Unlike MG132, BAY 11‐7082, a NF‐κB inhibitor, even reinforced the inhibitory effect of TNF‐α. Quantitative real‐time PCR (qRT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were used to investigate the role of Panx3 in inflammatory response of HDPCs. TNF‐α‐induced pro‐inflammatory cytokines, interleukin (IL)‐1β and IL‐6, were significantly lessened when Panx3 was overexpressed in HDPCs. Conversely, Panx3 knockdown exacerbated the expression of pro‐inflammatory cytokines. Moreover, Western blot, dual‐luciferase reporter assay, immunofluorescence staining, qRT‐PCR and ELISA results showed that Panx3 participated in dental pulp inflammation in a NF‐κB‐dependent manner. These findings suggested that Panx3 has a defensive role in dental pulp inflammation, serving as a potential target to be exploited for the intervention of human dental pulp inflammation.

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Section: Tnf-a Concentration Dependency Of Panx3 Expression In Hdpcssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

Song

Sun

Wang

et al. 2016

J Cellular Molecular Medi

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“…This study provides evidence that Panx3 is an ATP release channel similar to Panx1, supporting two claims of ATP release via Panx3, suggestive of channel function, in cultured ATDC5 skeletal cells (Iwamoto et al, 2010 ) and human odontoblast-like cells (Fu et al, 2015 ). Further, Panx3, like Panx1, takes up dye in a linear relationship with protein expression, albeit at different efficiency, and in response to known Panx1 blockers.…”

Section: Discussionsupporting

confidence: 78%

A Potential Compensatory Role of Panx3 in the VNO of a Panx1 Knock Out Mouse Model

Whyte-Fagundes

Kurtenbach

Zoidl

et al. 2018

Front. Mol. Neurosci.

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Pannexins (Panx) are integral membrane proteins, with Panx1 being the best-characterized member of the protein family. Panx1 is implicated in sensory processing, and knockout (KO) animal models have become the primary tool to investigate the role(s) of Panx1 in sensory systems. Extending previous work from our group on primary olfaction, the expression patterns of Panxs in the vomeronasal organ (VNO), an auxiliary olfactory sense organ with a role in reproduction and social behavior, were compared. Using qRT-PCR and Immunohistochemistry (IHC), we confirmed the loss of Panx1, found similar Panx2 expression levels in both models, and a significant upregulation of Panx3 in mice with a global ablation of Panx1. Specifically, Panx3 showed upregulated expression in nerve fibers of the non-sensory epithelial layer in juvenile and adult KO mice and in the sensory layer of adults, which overlaps with Panx1 expression areas in WT populations. Since both social behavior and evoked ATP release in the VNO was not compromised in KO animals, we hypothesized that Panx3 could compensate for the loss of Panx1. This led us to compare Panx1 and Panx3 channels in vitro, demonstrating similar dye uptake and ATP release properties. Outcomes of this study strongly suggest that Panx3 may functionally compensate for the loss of Panx1 in the VNO of the olfactory system, ensuring sustained chemosensory processing. This finding extends previous reports on the upregulation of Panx3 in arterial walls and the skin of Panx1 KO mice, suggesting that roles of Panx1 warrant uncharacterized safeguarding mechanisms involving Panx3.

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“…However, the molecular mechanism of this cellular event remains elusive. One possible explanation is that Panx3 functions as a hemichannel mediating ATP release from the cytoplasm into extracellular environments [33]. Likewise, extracellular ATP could activate the ERK signaling pathway [34][35][36], partially explaining the promotive implication of Panx3 on the ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects

Song

Sun

Huang

et al. 2017

Cell Physiol Biochem

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Key WordsPannexin3 • Human dental pulp-derived mesenchymal stromal cells • Wnt/β-catenin • ERK • Critical-sized bone defect • Bone tissue engineering Abstract:Background/Aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multilineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation.

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Expression of Pannexin3 in human odontoblast-like cells and its hemichannel function in mediating ATP release

Cited by 13 publications

References 39 publications

Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

A Potential Compensatory Role of Panx3 in the VNO of a Panx1 Knock Out Mouse Model

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects

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