Transient receptor potential melastatin 4 channel is required for rat dental pulp stem cell proliferation and survival

Tran, Tuyet-Minh; Stovall, Kelsie E; Suantawee, Tanyawan; Hu, Yue; Yao, Shaomian; Li, Yang; Cheng, Hong-In

doi:10.1111/cpr.12360

Cited by 13 publications

(11 citation statements)

References 32 publications

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“…3 ). The larger Ca 2+ load associated with Biodentine may act through increased Ca 2+ entry into the cell, possibly via Cav1.2 L-type Ca 2+ channels 24 , 25 , ORAI1, an essential pore subunit of store-operated Ca 2+ entry (SOCE) channels in stem cells 26 or TRPM4 channels 27 . Increased Ca 2+ entry is followed by intracellular cycling between the cytoplasm, ER Ca 2+ stores and mitochondria in mesenchymal stem cells, thus leading to the observed Ca 2+ dynamics 28 , 29 .…”

Section: Discussionmentioning

confidence: 99%

The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome

Rathinam

Govindarajan

Rajasekharan

et al. 2021

Sci Rep

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Calcium (Ca2+) signalling plays an indispensable role in dental pulp and dentin regeneration, but the Ca2+ responses of human dental pulp stem cells (hDPSCs) stimulated with tricalcium silicate-based (TCS-based) dental biomaterials remains largely unexplored. The objective of the present study was to identify and correlate extracellular Ca2+ concentration, intracellular Ca2+ dynamics, pH, cytotoxicity, gene expression and mineralization ability of human dental pulp stem cells (hDPSCs) stimulated with two different TCS-based biomaterials: Biodentine and ProRoot white MTA. The hDPSCs were exposed to the biomaterials, brought in contact with the overlaying medium, with subsequent measurements of extracellular Ca2+ and pH, and intracellular Ca2+ changes. Messenger RNA expression (BGLAP, TGF-β, MMP1 and BMP2), cytotoxicity (MTT and TUNEL) and mineralization potential (Alizarin red and Von Kossa staining) were then evaluated. Biodentine released significantly more Ca2+ in the α-MEM medium than ProRoot WMTA but this had no cytotoxic impact on hDPSCs. The larger Biodentine-linked Ca2+ release resulted in altered intracellular Ca2+ dynamics, which attained a higher maximum amplitude, faster rise time and increased area under the curve of the Ca2+ changes compared to ProRoot WMTA. Experiments with intracellular Ca2+ chelation, demonstrated that the biomaterial-triggered Ca2+ dynamics affected stem cell-related gene expression, cellular differentiation and mineralization potential. In conclusion, biomaterial-specific Ca2+ dynamics in hDPSCs determine differentiation and mineralization outcomes, with increased Ca2+ dynamics enhancing mineralization.

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Section: Discussionmentioning

confidence: 99%

The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome

Rathinam

Govindarajan

Rajasekharan

et al. 2021

Sci Rep

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“…Anticancer drugs may involve changes in Ca 2+ signaling [53,54]; moreover, membrane transport proteins contribute to chemoresistance in several types of cancer [55]. Although TRPM4 is nonpermeable to Ca 2+ , Na + influx via TRPM4 decreases membrane potential and results in a decrease in intracellular Ca 2+ signaling in many different cells, including rat dental pulp stem cells, various immune cells, and cancer cells [2,[12][13][14]41,56,57]. However, an increase in SOCE by TRPM4 expression has also been observed [35,58].…”

Section: General Mechanisms Of Trpm4mentioning

confidence: 99%

TRPM4 in Cancer—A New Potential Drug Target

2021

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Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.

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“…Intraflagellar transport 80 (IFT80) was also shown to play crucial roles in the proliferation of mouse DPSCs via regulating the FGF–PI3K–AKT signaling pathway [ 27 ]. Moreover, transient receptor potential melastatin 4 channel was revealed to be involved in the proliferation and survival of rat DPSCs by controlling intracellular Ca 2+ signals [ 28 ]. Furthermore, Gao et al demonstrated that the growth capacity of PDLSCs was associated with JNK and p38 MAPK pathways, whereas the proliferation of DPSCs appeared to be dependent on ERK1/2 MAPK pathway activation [ 29 ].…”

Section: Self-renewal and High Growth Capacity Of Dpscs And Shedsmentioning

confidence: 99%

Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy

Yoshida

Tomokiyo

Hasegawa

et al. 2020

Biology

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Mesenchymal stem cells (MSCs) have the capacity for self-renewal and multilineage differentiation potential, and are considered a promising cell population for cell-based therapy and tissue regeneration. MSCs are isolated from various organs including dental pulp, which originates from cranial neural crest-derived ectomesenchyme. Recently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have been isolated from dental pulp tissue of adult permanent teeth and deciduous teeth, respectively. Because of their MSC-like characteristics such as high growth capacity, multipotency, expression of MSC-related markers, and immunomodulatory effects, they are suggested to be an important cell source for tissue regeneration. Here, we review the features of these cells, their potential to regenerate damaged tissues, and the recently acquired understanding of their potential for clinical application in regenerative medicine.

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Transient receptor potential melastatin 4 channel is required for rat dental pulp stem cell proliferation and survival

Abstract: Rat DPSCs have stem cell characteristics and functional TRPM4 channels that are required for proliferation and survival. These data suggest that the shape and frequency of intracellular Ca signals may mediate stem cell proliferation and survival.

Cited by 13 publications

References 32 publications

The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome

The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome

TRPM4 in Cancer—A New Potential Drug Target

Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy

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