Activation of Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Channels Promotes Odontogenic Differentiation of Human Dental Pulp Cells

Lou, Yonggen; Liu, Yangqiu; Zhao, Jiange; Tian, Wei; Xu, Na; Zang, Chengcheng; Que, Kehua

doi:10.1016/j.joen.2021.06.007

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…Our previous study and this study demonstrated that hDPSC-K4DT cells retained the original differentiation abilities of human dental pulp cells. Furthermore, consistent with previous reports 23 , 36 , TRPA1 was highly expressed in hDPSC-K4DT cells, and TRPA1 expression was elevated along with their osteogenic differentiation. These results indicate that hDPSC-K4DT cells are a useful in vitro tool for studying the cytotoxicity of HEMA and can be used for the evaluation of the relationship between cytotoxicity and TRPA1 channels.…”

Section: Discussionsupporting

confidence: 92%

“…The channel is predominantly expressed in human dental pulp, and its expression is significantly higher in painful pulp than in normal pulp 21 . Recent studies have reported that TRPA1 expression is upregulated in odontoblasts aligned along tertiary dentin formed under carious lesions 22 , 23 . Tertiary dentin is produced by odontoblasts in response to external stimuli.…”

Section: Introductionmentioning

confidence: 99%

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2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

Orimoto

Kitamura

Ono

2022

Sci Rep

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Extracellular ATP (adenosine triphosphate) and transient receptor potential ankyrin 1 (TRPA1) channels are involved in calcium signaling in odontoblasts and dental pain. The resin monomer 2-hydroxyethyl methacrylate (HEMA), used in dental restorative procedures, is related to apoptotic cell death via oxidative stress. Although the TRPA1 channel is highly sensitive to reactive oxygen species (ROS), the effect of HEMA-induced ROS on ATP release to the extracellular space and the TRPA1 channel has not been clarified in human dental pulp. In this study, we investigated the extracellular ATP signaling and TRPA1 activation by HEMA-derived ROS in immortalized human dental pulp cells (hDPSC-K4DT). Among the ROS-sensitive TRP channels, TRPA1 expression was highest in undifferentiated hDPSC-K4DT cells, and its expression levels were further enhanced by osteogenic differentiation. In differentiated hDPSC-K4DT cells, 30 mM HEMA increased intracellular ROS production and ATP release, although 3 mM HEMA had no effect. Pretreatment with the free radical scavenger PBN (N-tert-butyl-α-phenylnitrone) or TRPA1 antagonist HC-030031 suppressed HEMA-induced responses. These results suggest that ROS production induced by a higher dose of HEMA activates the TRPA1 channel in human dental pulp cells, leading to ATP release. These findings may contribute to the understanding of the molecular and cellular pathogenesis of tertiary dentin formation and pain in response to dental biomaterials.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

Orimoto

Kitamura

Ono

2022

Sci Rep

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“…Among various types of receptors in the odontoblast membrane [ 41 ], mechano-sensitive ion channels (MICs), including PIEZO and TRP channels within the plasma membrane of odontoblasts, are known to be responsible for mechano-sensing [ 46 ] ( Table 1 ). Upon exposure to mechanical stimuli, plasma membranes deform, and the altered membrane tension gates those MICs, subsequently generating intracellular calcium ion influx and initiating mechano-signal transduction [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] ( Figure 1 C). Various downstream cascade signaling pathways are activated, eventually promoting cells to respond to the mechanical stimuli accordingly [ 49 , 55 , 56 , 57 , 58 , 59 ] ( Figure 1 D).…”

Section: Dentin Mechano-sensingmentioning

confidence: 99%

“…Primary cultured OBs express TRP channels, contributing to mechano-sensitive sensory transmission [50] TRPV1 -cAMP-mediated crosstalk between CB1 and TRPV1 in OBs leads to Ca 2+ intracellular accumulation -Functional TRPV1-NCX coupling facilitates Ca 2+ extrusion, drives dentinogenesis, and maintains intracellular calcium homeostasis [51] TRPV1, TRPA1 -These channels exhibit upregulation during the odontogenic differentiation of hDPSCs -Modulate odontogenic differentiation by regulating intercellular Ca 2+ concentration [52] Temperature shock (cold) PIEZO1 PIEZO1/TRPA1-pannexin-1-P2X3 receptor axis pathway Mediates sensory transduction in dentinal sensitivity between odontoblasts and neurons [68] TRPA1, TRPM8 Calcium signaling pathway Increased [Ca 2+ ]i in response to TRPA1 and TRPM8 activation, majoring physiological importance for pulpal homeostasis [53] TRPC5 TRPC5 is a cold sensor in intact teeth and originates the transduction in odontoblasts [54] MIC, mechanical ion channels; hPDLCs, human periodontal ligament cells; HP, hydrostatic pressure; MSC, Menachem stem cells; SHEDs, stem cells from human exfoliated deciduous teeth; OBs, odontoblasts; LIPUS, Low-intensity pulsed ultrasound; DPSCs, dental pulp stem cells; NCX, Na + -Ca 2+ exchangers; TG, trigeminal ganglia neurons; DRG, dorsal root ganglia neurons; hDPFs, human dental pulp fibroblasts.…”

Section: Piezo1mentioning

confidence: 99%

Dentin Mechanobiology: Bridging the Gap between Architecture and Function

Fu,

Kim

2024

IJMS

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It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin’s unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin’s architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin’s physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin’s physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.

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“…Previous studies have investigated the underlying mechanisms of the involvement of DPSCs in dentinogenesis, including epigenetic mechanisms [6][7][8][9][10], involvement of growth factors [11][12][13][14], and iron homeostasis [15][16][17][18][19]. Dentinogenesis and osteogenesis share many similarities, including genes that regulate odontoblastic and osteogenic differentiation, conversion processes from unmineralized predentin to dentin and osteoid to bone, and mineralization mechanisms, such as hormonal regulation [20,21].…”

Section: Introductionmentioning

confidence: 99%

Promotive Effect of FBXO32 on the Odontoblastic Differentiation of Human Dental Pulp Stem Cells

Liu

Huang

et al. 2023

IJMS

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Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) is crucial for the intricate formation and repair processes in dental pulp. Until now, the literature is not able to demonstrate the role of ubiquitination in the odontoblastic differentiation of hDPSCs. This study investigated the role of F-box-only protein 32 (FBXO32), an E3 ligase, in the odontoblastic differentiation of hDPSCs. The mRNA expression profile was obtained from ribonucleic acid sequencing (RNA-Seq) data and analyzed. Immunofluorescence and immunohistochemical staining identify the FBXO32 expression in human dental pulp and hDPSCs. Small-hairpin RNA lentivirus was used for FBXO32 knockdown and overexpression. Odontoblastic differentiation of hDPSCs was determined via alkaline phosphatase activity, Alizarin Red S staining, and mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction and Western blotting. Furthermore, subcutaneous transplantation in nude mice was performed to evaluate the role of FBXO32 in mineralization in vivo using histological analysis. FBXO32 expression was upregulated in the odontoblast differentiated hDPSCs as evidenced by RNA-Seq data analysis. FBXO32 was detected in hDPSCs and the odontoblast layer of the dental pulp. Increased FBXO32 expression in hDPSCs during odontoblastic differentiation was confirmed. Through lentivirus infection method, FBXO32 downregulation in hDPSCs attenuated odontoblastic differentiation in vitro and in vivo, whereas FBXO32 upregulation promoted the hDPSCs odontoblastic differentiation, without affecting proliferation and migration. This study demonstrated, for the first time, the promotive role of FBXO32 in regulating the odontoblastic differentiation of hDPSCs, thereby providing novel insights into the regulatory mechanisms during odontoblastic differentiation in hDPSCs.

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Activation of Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Channels Promotes Odontogenic Differentiation of Human Dental Pulp Cells

Cited by 7 publications

References 28 publications

2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

Dentin Mechanobiology: Bridging the Gap between Architecture and Function

Promotive Effect of FBXO32 on the Odontoblastic Differentiation of Human Dental Pulp Stem Cells

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