TRPM8 Channel Promotes the Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells

Abstract

Various families of ion channels have been characterized in mesenchymal stem cells (MSCs), including some members of transient receptor potential (TRP) channels family. TRP channels are involved in critical cellular processes as differentiation and cell proliferation. Here, we analyzed the expression of TRPM8 channel in human bone marrow MSCs (hBM-MSCs), and its relation with osteogenic differentiation. Patch-clamp recordings showed that hBM-MSCs expressed outwardly rectifying currents which were increased by exposure to 500 μM menthol and were partially inhibited by 10 μM of BCTC, a TRPM8 channels antagonist. Additionally, we have found the expression of TRPM8 by RT-PCR and western blot. We also explored the TRPM8 localization in hBM-MSCs by immunofluorescence using confocal microscopy. Remarkably, hBM-MSCs treatment with 100 μM of menthol or 10 μM of icilin, TRPM8 agonists, increases osteogenic differentiation. Conversely, 20 μM of BCTC, induced a decrease of osteogenic differentiation. These results suggest that TRPM8 channels are functionally active in hBM-MSCs and have a role in cell differentiation.

Therapeutic potential of TRPM8 channels in cancer treatment

“…In some of these tissues, channel overexpression has been associated with events characteristic of tumors, like cell migration and invasion. However, in some cancers, it has been reported that TRPM8 channel activation is enough to promote proliferation and migration in some tissues but decrease these processes in others ( Liu J. F. et al, 2018 ; Lan et al, 2019 ; Liu et al, 2020 ; Henao et al, 2021 ; Liu J. J. et al, 2022 ). In the next section, we will describe the reported functions of TRPM8 in diverse cancers.…”

New Insights into TRP Ion Channels in Stem Cells

“…In human bone marrow MSCs, TRPM8 shows specific expression in the ER, suggesting that its main function may be related to the release of intracellular Ca 2+ . In addition, activation of TRPM8 promotes osteogenic differentiation of human MSCs [ 14 ]. In rat dental follicle stem cells, functional expression of TRPM4 facilitates adipogenesis via Ca 2+ signaling [ 77 ].…”

“…Given the functional properties of TRP channels and their expressions in stem cells, it is not surprising that they may participate in regulating stem cell physiology and differentiation. Indeed, recent studies have found that TRP ion channels are implicated in stem cells [ 13 , 14 , 15 ]. This review summarizes the expression patterns of TRP channels in various stem cells, with particular focus on the potential roles TRP channels play in regulating stem cell physiology and pathophysiology.…”

Polythiophene-mediated light modulation of membrane potential and calcium signalling in human adipose-derived stem/stromal cells

“…30 Furthermore, in endothelial cell models a similar effect was attributed to spatially-confined modulation of the transient receptor potential (TRP) vanilloid channel TRPV1, as mainly due to a photoelectrochemical process. 33,42 Interestingly, pH and temperature dependent channels, including canonical TRP (TRPC), melastatin TRP (TRPM), and tandem pore-class K + (TREK) channels, are also expressed in hASC, and they play critical roles in differentiation, migration and proliferation, 43,44 as much as K + channels. 45 However, future ad hoc pharmacological studies would be needed to unambiguously attribute the variation in the hASC membrane potential to specific ionic channels conductivity, and to unravel any influence on cell activity.…”