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中华口腔医学研究杂志(电子版) ›› 2024, Vol. 18 ›› Issue (01) : 54 -60. doi: 10.3877/cma.j.issn.1674-1366.2024.01.009

综述

机械敏感离子通道在牙源性细胞中作用的研究进展
徐志清, 杜宇†()   
  1. 中山大学附属口腔医院，光华口腔医学院，广东省口腔医学重点实验室，广东省口腔疾病临床医学研究中心，广州　510055
  • 收稿日期:2023-07-20 出版日期:2024-02-01
  • 通信作者: 杜宇

Research advances on the role of mechanosensitive ion channels in odontogenic cells

Zhiqing Xu, Yu Du†()   

  1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangdong Provincial Clinical Research Center of Oral Diseases, Guangzhou 510055, China
  • Received:2023-07-20 Published:2024-02-01
  • Corresponding author: Yu Du
  • Supported by:
    Natural Science Foundation of Guangdong Province(2021A1515010845); Medical Scientific Research Foundation of Guangdong Province(A2022126)
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引用本文：

徐志清, 杜宇. 机械敏感离子通道在牙源性细胞中作用的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2024, 18(01): 54-60.

Zhiqing Xu, Yu Du. Research advances on the role of mechanosensitive ion channels in odontogenic cells[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2024, 18(01): 54-60.

机械敏感离子通道（MS离子通道）是一类能感知机械应力的重要蛋白，将细胞外机械刺激信号转化为电化学信号，导致离子跨膜流通，继而传递至胞内调控下游靶基因。牙源性细胞胞膜表面有多种MS离子通道表达，但其如何调控细胞功能和具体机制仍不明确。本文就MS离子通道的分类及其在牙源性细胞的表达和功能作一综述。

关键词: 机械敏感通道, 牙再生, 压电离子通道, 瞬时受体电位离子通道

As crucial proteins in sensing mechanical stress, mechanosensitive (MS) ion channels could transform external mechanical stimuli into electrochemical signals, enabling ion transmembrane movement. This movement signals the intracellular regulation of target genes. While various MS ion channels are present in odontogenic cell membranes, their roles in the cellular regulation and the exact mechanisms are still not fully understood. This review focused on the classification, expression, and functionality of MS ion channels in odontogenic cells.

Key words: Mechanosensitive channels, Tooth regeneration, PIEZO, TRP channels
[1]
Huang H，Kamm RD，Lee RT. Cell mechanics and mechanotransduction：Pathways，probes，and physiology[J]. 2004，287（1）：C1-C11. DOI：10.1152/ajpcell.00559.2003.
[2]
Matthews BD，Thodeti CK，Tytell JD，et al. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins[J]. Integr Biol（Camb），2010，2（9）：435-442. DOI：10.1039/c0ib00034e.
[3]
Anishkin A，Kung C. Stiffened lipid platforms at molecular force foci[J]. Proc Natl Acad Sci U S A，2013，110（13）：4886-4892. DOI：10.1073/pnas.1302018110.
[4]
Sugimoto A，Miyazaki A，Kawarabayashi K，et al. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells [J]. Sci Rep，2017，7（1）：17696. DOI：10.1038/s41598-017-18089-0.
[5]
Miyazaki A，Sugimoto A，Yoshizaki K，et al. Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1[J]. Sci Rep，2019，9（1）：14762. DOI：10.1038/s41598-019-51381-9.
[6]
Xing Y，Yang B，He Y，et al. Effects of mechanosensitive ion channel Piezo1 on proliferation and osteogenic differentiation of human dental follicle cells[J]. Ann Anat，2022，239：151847. DOI：10.1016/j.aanat.2021.151847.
[7]
Gao Q，Cooper PR，Walmsley AD，et al. Role of Piezo channels in ultrasound-stimulated dental stem cells[J]. J Endod，2017，43（7）：1130-1136. DOI：10.1016/j.joen.2017.02.022.
[8]
Magloire H，Lesage F，Couble ML，et al. Expression and localization of TREK-1 K+ channels in human odontoblasts[J]. J Dent Res，2003，82（7）：542-545. DOI：10.1177/154405910308200711.
[9]
Wen W，Que K，Zang C，et al. Expression and distribution of three transient receptor potential vanilloid（TRPV）channel proteins in human odontoblast-like cells[J]. J Mol Histol，2017，48（5-6）：367-377. DOI：10.1007/s10735-017-9735-2.
[10]
Won J，Vang H，Kim JH，et al. TRPM7 mediates mechanosensitivity in adult rat odontoblasts[J]. J Dent Res，2018，97（9）：1039-1046. DOI：10.1177/0022034518759947.
[11]
Matsunaga M，Kimura M，Ouchi T，et al. Mechanical stimulation-induced calcium signaling by Piezo1 channel activation in human odontoblast reduces dentin mineralization[J]. Front Physiol，2021，12：704518. DOI：10.3389/fphys.2021.704518.
[12]
Cox CD，Bavi N，Martinac B. Biophysical principles of ion-channel-mediated mechanosensory transduction[J]. Cell reports，2019，29（1）：1-12. DOI：10.1016/j.celrep.2019.08.075.
[13]
Syeda R，Florendo MN，Cox CD，et al. Piezo1 channels are inherently mechanosensitive[J]. Cell reports，2016，17（7）：1739-1746. DOI：10.1016/j.celrep.2016.10.033.
[14]
Suchyna TM. Piezo channels and GsMTx4：Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology[J]. Prog Biophys Mol Biol，2017，130（Pt B）：244-253. DOI：10.1016/j.pbiomolbio.2017.07.011.
[15]
Cox CD，Bae C，Ziegler L，et al. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension[J]. Nat Commun，2016，7：10366. DOI：10.1038/ncomms10366.
[16]
Retailleau K，Duprat F，Arhatte M，et al. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling [J]. Cell Rep，2015，13（6）：1161-1171. DOI：10.1016/j.celrep.2015.09.072.
[17]
Gottlieb PA，Bae C，Sachs F. Gating the mechanical channel Piezo1：A comparison between whole-cell and patch recording [J]. Channels（Austin），2012，6（4）：282-289. DOI：10.4161/chan.21064.
[18]
Douguet D，Honoré E. Mammalian mechanoelectrical transduction：Structure and function of force-gated ion channels[J]. Cell，2019，179（2）：340-354. DOI：10.1016/j.cell.2019.08.049.
[19]
Ranade SS，Syeda R，Patapoutian A. Mechanically activated ion channels[J]. Neuron，2015，87（6）：1162-1179. DOI：10.1016/j.neuron.2015.08.032.
[20]
Coste B，Mathur J，Schmidt M，et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels[J]. Science，2010，330（6000）：55-60. DOI：10.1126/science.1193270.
[21]
Lee W，Leddy HA，Chen Y，et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage[J]. Proc Natl Acad Sci U S A，2014，111（47）：E5114-E5122. DOI：10.1073/pnas.1414298111.
[22]
Xu BY，Jin Y，Ma XH，et al. The potential role of mechanically sensitive ion channels in the physiology，injury，and repair of articular cartilage[J]. J Orthop Surg（Hong Kong），2020，28（3）：2309499020950262. DOI：10.1177/2309499020950262.
[23]
Corey DP，García-Añoveros J，Holt JR，et al. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells[J]. Nature，2004，432（7018）：723-730. DOI：10.1038/nature03066.
[24]
Suzuki M，Mizuno A，Kodaira K，et al. Impaired pressure sensation in mice lacking TRPV4[J]. J Biol Chem，2003，278（25）：22664-22668. DOI：10.1074/jbc.M302561200.
[25]
Kamkin AG，Kiseleva IS，Iarygin VN. Mechanosensitive ion channels[J]. Usp Fiziol Nauk，2002，33（3）：3-37.
[26]
Venkatachalam K，Montell C. TRP channels[J]. Annu Rev Biochem，2007，76：387-417. DOI：10.1146/annurev.biochem.75.103004.142819.
[27]
Tazawa K，Ikeda H，Kawashima N，et al. Transient receptor potential melastatin（TRPM）8 is expressed in freshly isolated native human odontoblasts[J]. Arch Oral Biol，2017，75：55-61. DOI：10.1016/j.archoralbio.2016.12.007.
[28]
Kärki T，Tojkander S. TRPV protein family-from mechanosensing to cancer invasion[J]. Biomolecules，2021，11（7）：1019. DOI：10.3390/biom11071019.
[29]
Talavera K，Startek JB，Alvarez-Collazo J，et al. Mammalian transient receptor potential TRPA1 channels：From structure to disease[J]. Physiol Rev，2020，100（2）：725-803. DOI：10.1152/physrev.00005.2019.
[30]
Enyedi P，Czirják G. Molecular background of leak K+ currents：Two-pore domain potassium channels[J]. Physiol Rev，2010，90（2）：559-605. DOI：10.1152/physrev.00029.2009.
[31]
Lengyel M，Enyedi P，Czirják G. Negative influence by the force：Mechanically induced hyperpolarization via K2P background potassium channels[J]. Int J Mol Sci，2021，22（16）：9062. DOI：10.3390/ijms22169062.
[32]
Brohawn SG，Su Z，MacKinnon R. Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels[J]. Proc Natl Acad Sci U S A，2014，111（9）：3614-3619. DOI：10.1073/pnas.1320768111.
[33]
Aguan DW，George AG，Richard A，et al. International union of pharmacology. LII. nomenclature and molecular relationships of calcium-activated potassium channels[J]. Pharmacol Rev，2005，57（4）：463. DOI：10.1124/pr.57.4.9.
[34]
Koh SD，Sanders KM. Stretch-dependent potassium channels in murine colonic smooth muscle cells[J]. J Physiol，2001，533（Pt 1）：155-163. DOI：10.1111/j.1469-7793.2001.0155b.x.
[35]
Balemans D，Boeckxstaens GE，Talavera K，et al. Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity[J]. Am J Physiol Gastrointest Liver Physiol，2017，312（6）：G635-G648. DOI：10.1152/ajpgi.00401.2016.
[36]
Wang W，Huang H，Hou D，et al. Mechanosensitivity of STREX-lacking BKCa channels in the colonic smooth muscle of the mouse[J]. Am J Physiol Gastrointest Liver Physiol，2010，299（6）：G1231-G1240. DOI：10.1152/ajpgi.00268.2010.
[37]
MacLean DM，Soto E. Editorial：ASICs：Structure，function，and pharmacology[J]. Front Physiol，2022，13：831830. DOI：10.3389/fphys.2022.831830.
[38]
Ruan N，Tribble J，Peterson AM，et al. Acid-sensing ion channels and mechanosensation[J]. Int J Mol Sci，2021，22（9）：4810. DOI：10.3390/ijms22094810.
[39]
Magloire H，Couble ML，Thivichon-Prince B，et al. Odontoblast：A mechano-sensory cell[J]. J Exp Zool B Mol Dev Evol，2009，312b（5）：416-424. DOI：10.1002/jez.b.21264.
[40]
Shibukawa Y，Sato M，Kimura M，et al. Odontoblasts as sensory receptors：Transient receptor potential channels，pannexin-1，and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction[J]. Pflugers Arch，2015，467（4）：843-863. DOI：10.1007/s00424-014-1551-x.
[41]
梁春云，吴声，胡德渝，等.瞬时感受器电位香草酸受体3离子通道蛋白在人成牙本质细胞中的表达[J].中华口腔医学杂志，2013，48（11）：679-682. DOI：10.3760/cma.j.issn.1002-0098.2013.11.009.
[42]
Seux D，Joffre A，Fosset M，et al. Immunohistochemical localization of L-type calcium channels in the developing first molar of the rat during odontoblast differentiation[J]. Arch Oral Biol，1994，39（2）：167-170. DOI：10.1016/0003-9969(94)90113-9.
[43]
Allard B，Couble ML，Magloire H，et al. Characterization and gene expression of high conductance calcium-activated potassium channels displaying mechanosensitivity in human odontoblasts [J]. J Biol Chem，2000，275（33）：25556-25561. DOI：10.1074/jbc.M002327200.
[44]
Sato M，Ogura K，Kimura M，et al. Activation of mechanosensitive transient receptor potential/Piezo channels in odontoblasts generates action potentials in cocultured isolectin B4-negative medium-sized trigeminal ganglion neurons[J]. J Endod，2018，44（6）：984-991.e2. DOI：10.1016/j.joen.2018.02.020.
[45]
Cho YS，Han HM，Jeong SY，et al. Expression of Piezo1 in the trigeminal neurons and in the axons that innervate the dental pulp [J]. Front Cell Neurosci，2022，16：945948. DOI：10.3389/fncel.2022.945948.
[46]
Bernal L，Sotelo-Hitschfeld P，König C，et al. Odontoblast TRPC5 channels signal cold pain in teeth[J]. Science advances，2021，7（13）：eabf5567. DOI：10.1126/sciadv.abf5567.
[47]
Okumura R，Shima K，Muramatsu T，et al. The odontoblast as a sensory receptor cell？The expression of TRPV1（VR-1）channels[J]. Arch Histol Cytol，2005，68（4）：251-257. DOI：10.1679/aohc.68.251.
[48]
Tsumura M，Sobhan U，Muramatsu T，et al. TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium-calcium exchangers in rat odontoblasts[J]. Cell calcium，2012，52（2）：124-136. DOI：10.1016/j.ceca.2012.05.002.
[49]
Sato M，Sobhan U，Tsumura M，et al. Hypotonic-induced stretching of plasma membrane activates transient receptor potential vanilloid channels and sodium-calcium exchangers in mouse odontoblasts[J]. J Endod，2013，39（6）：779-787. DOI：10.1016/j.joen.2013.01.012.
[50]
Son AR，Yang YM，Hong JH，et al. Odontoblast TRP channels and thermo/mechanical transmission[J]. J Dent Res，2009，88（11）：1014-1019. DOI：10.1177/0022034509343413.
[51]
Kim YS，Kim TH，McKemy DD，et al. Expression of vesicular glutamate transporters in transient receptor potential melastatin 8 （TRPM8）-positive dental afferents in the mouse[J]. Neuroscience，2015，303：378-388. DOI：10.1016/j.neuroscience.2015.07.013.
[52]
Guo L，Berry JE，Somerman MJ，et al. A novel method to isolate odontoblasts from rat incisor[J]. Calcif Tissue Int，2000，66（3）：212-216. DOI：10.1007/pl00005837.
[53]
Sun X，Dong S，Kato H，et al. Mitochondrial calcium-triggered oxidative stress and developmental defects in dopaminergic neurons differentiated from deciduous teeth-derived dental pulp stem cells with MFF insufficiency[J]. Antioxidants（Basel），2022，11（7）：1361. DOI：10.3390/antiox11071361.
[54]
El Karim IA，Linden GJ，Curtis TM，et al. Human odontoblasts express functional thermo-sensitive TRP channels：Implications for dentin sensitivity[J]. Pain，2011，152（10）：2211-2223. DOI：10.1016/j.pain.2010.10.016.
[55]
Egbuniwe O，Grover S，Duggal AK，et al. TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release[J]. J Dent Res，2014，93（9）：911-917. DOI：10.1177/0022034514544507.
[56]
Lin Y，Cheng T，Zhu S，et al. mRNA and long non-coding RNA expression profiling of human periodontal ligament cells under tension loading[J]. Eur J Orthod，2021，43（6）：698-707. DOI：10.1093/ejo/cjab043.
[57]
de Jong T，Bakker AD，Everts V，et al. The intricate anatomy of the periodontal ligament and its development：Lessons for periodontal regeneration[J]. J Periodontal Res，2017，52（6）：965-974. DOI：10.1111/jre.12477.
[58]
康婷，黄世友，李鹏，等. Piezos离子通道在大鼠牙周组织中表达的实验研究[J].牙体牙髓牙周病学杂志，2014，24（5）：269-273. DOI：10.15956/j.cnki.chin.j.conserv.dent.2014.05.006.
[59]
Jin Y，Li J，Wang Y，et al. Functional role of mechanosensitive ion channel Piezo1 in human periodontal ligament cells[J]. Angle Orthod，2015，85（1）：87-94. DOI：10.2319/123113-955.1.
[60]
Shen Y，Pan Y，Guo S，et al. The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction[J]. Mol Med Rep，2020，21（5）：2113-2122. DOI：10.3892/mmr.2020.11006.
[61]
Ohara A，Saeki Y，Nishikawa M，et al. Single-channel recordings of TREK-1 K+ channels in periodontal ligament fibroblasts[J]. J Dent Res，2006，85（7）：664-669. DOI：10.1177/154405910608500716.
[62]
Song Z，Chen L，Guo J，et al. The role of transient receptor potential cation channel，subfamily C，member 1 in the odontoblast-like differentiation of human dental pulp cells[J]. J Endod，2017，43（2）：315-320. DOI：10.1016/j.joen.2016.10.021.
[63]
Mousawi F，Peng H，Li J，et al. Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling[J]. Stem Cells，2020，38（3）：410-421. DOI：10.1002/stem.3114.
[64]
Yang X，Song Z，Chen L，et al. Role of transient receptor potential channel 6 in the odontogenic differentiation of human dental pulp cells[J]. Exp Ther Med，2017，14（1）：73-78. DOI：10.3892/etm.2017.4471.
[65]
Kwon M，Baek SH，Park CK，et al. Single-cell RT-PCR and immunocytochemical detection of mechanosensitive transient receptor potential channels in acutely isolated rat odontoblasts[J]. Arch Oral Biol，2014，59（12）：1266-1271. DOI：10.1016/j.archoralbio.2014.07.016.
[66]
Wiesmann HP，Tkotz T，Joos U，et al. Magnesium in newly formed dentin mineral of rat incisor[J]. J Bone Miner Res，1997，12（3）：380-383. DOI：10.1359/jbmr.1997.12.3.380.
[67]
Harrison A，Lin S，Pounder N，et al. Mode & mechanism of low intensity pulsed ultrasound（LIPUS）in fracture repair[J]. Ultrasonics，2016，70：45-52. DOI：10.1016/j.ultras.2016.03.016.
[68]
姚欢，潘华锋，郑妍，等.机械敏感离子通道Trpm7在LIPUS促进牙髓间充质干细胞成骨分化中的作用机制的研究[J].中国细胞生物学学报，2018，40（9）：1518-1525. DOI：10.11844/cjcb.2018.09.0129.
[69]
刘瑞瑞，徐小桥，洪珊珊，等.机械敏感离子通道Piezo在大鼠牙体缺损模型中的时空表达[C]//中华口腔医学会口腔生物医学专业委员会. 2019第九次全国口腔生物医学学术年会论文汇编，2019：29. DOI：10.26914/c.cnkihy.2019.024951.
[70]
Son GY，Yang YM，Park WS，et al. Hypotonic stress induces RANKL via transient receptor potential melastatin 3（TRPM3）and vaniloid 4（TRPV4）in human PDL cells[J]. J Dent Res，2015，94（3）：473-481. DOI：10.1177/0022034514567196.
[71]
Jiang Y，Guan Y，Lan Y，et al. Mechanosensitive Piezo1 in periodontal ligament cells promotes alveolar bone remodeling during orthodontic tooth movement[J]. Front Physiol，2021，12：767136. DOI：10.3389/fphys.2021.767136.
[72]
Nottmeier C，Lavicky J，Gonzalez Lopez M，et al. Mechanical-induced bone remodeling does not depend on Piezo1 in dentoalveolar hard tissue[J]. Sci Rep，2023，13（1）：9563. DOI：10.1038/s41598-023-36699-9.
[73]
Yeon KY，Chung G，Shin MS，et al. Adult rat odontoblasts lack noxious thermal sensitivity[J]. J Dent Res，2009，88（4）：328-332. DOI：10.1177/0022034509334100.
[74]
Addy M，Urquhart E. Dentine hypersensitivity：Its prevalence，aetiology and clinical management[J]. Dent Update，1992，19（10）：407-408，410-402.
[75]
Lee K，Lee BM，Park CK，et al. Ion channels involved in tooth pain[J]. Int J Mol Sci，2019，20（9）：2266. DOI：10.3390/ijms20092266.
[76]
Shibukawa Y，Sato M，Kimura M，et al. Odontoblasts as sensory receptors：Transient receptor potential channels，pannexin-1，and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction[J]. Pflugers Archiv，2015，467（4）：843-863. DOI：10.1007/s00424-014-1551-x.
[77]
Han HM，Jeong SY，Cho YS，et al. Expression of Piezo2 in the dental pulp，sensory root，and trigeminal ganglion and its coexpression with vesicular glutamate transporters[J]. J Endod，2022，48（11）：1407-1413. DOI：10.1016/j.joen.2022.07.012.
[78]
Sun XF，Qiao WW，Meng LY，et al. PIEZO1 Ion Channels Mediate Mechanotransduction in Odontoblasts[J]. J Endod，2022，48（6）：749-758. DOI：10.1016/j.joen.2022.02.005.
[79]
Bakri MM，Yahya F，Munawar KMM，et al. Transient receptor potential vanilloid 4（TRPV4）expression on the nerve fibers of human dental pulp is upregulated under inflammatory condition[J]. Arch Oral Biol，2018，89：94-98. DOI：10.1016/j.archoralbio.2018.02.011.
[80]
El Karim I，McCrudden MT，Linden GJ，et al. TNF-α-induced p38MAPK activation regulates TRPA1 and TRPV4 activity in odontoblast-like cells[J]. Am J Pathol，2015，185（11）：2994-3002. DOI：10.1016/j.ajpath.2015.07.020.
[81]
Haas ET，Rowland K，Gautam M. Tooth injury increases expression of the cold sensitive TRP channel TRPA1 in trigeminal neurons[J]. Arch Oral Biol，2011，56（12）：1604-1609. DOI：10.1016/j.archoralbio.2011.06.014.
[82]
Gao M，Long H，Ma W，et al. The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats [J]. Eur J Orthod，2016，38（6）：577-583. DOI：10.1093/ejo/cjv082.
[83]
Gao M，Yan X，Lu Y，et al. Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic tooth movement via acid-sensing ion channel 3[J]. Int J Oral Sci，2021，13（1）：18. DOI：10.1038/s41368-021-00124-6.
[84]
Hitomi Y，Suzuki A，Kawano Y，et al. Immunohistochemical detection of ENaCbeta in the terminal Schwann cells associated with the periodontal Ruffini endings of the rat incisor[J]. Biomed Res，2009，30（2）：113-119. DOI：10.2220/biomedres.30.113.
[85]
Rahman F，Harada F，Saito I，et al. Detection of acid-sensing ion channel 3（ASIC3）in periodontal Ruffini endings of mouse incisors[J]. Neurosci Lett，2011，488（2）：173-177. DOI：10.1016/j.neulet.2010.11.023.
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