PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation
Mechanical-loading and unloading can modify osteoblast functioning. Ca<sup>2+</sup> signaling is one of the earliest events in osteoblasts to induce a mechanical stimulus, thereby demonstrating the importance of the underlying mechanical sensors for the sensation. Here, we examined the m...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/19/4960 |
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| author | Maki Yoneda Hiroka Suzuki Noriyuki Hatano Sayumi Nakano Yukiko Muraki Ken Miyazawa Shigemi Goto Katsuhiko Muraki |
| author_facet | Maki Yoneda Hiroka Suzuki Noriyuki Hatano Sayumi Nakano Yukiko Muraki Ken Miyazawa Shigemi Goto Katsuhiko Muraki |
| author_sort | Maki Yoneda |
| collection | DOAJ |
| description | Mechanical-loading and unloading can modify osteoblast functioning. Ca<sup>2+</sup> signaling is one of the earliest events in osteoblasts to induce a mechanical stimulus, thereby demonstrating the importance of the underlying mechanical sensors for the sensation. Here, we examined the mechano-sensitive channels PIEZO1 and TRPV4 were involved in the process of mechano-sensation in the osteoblastic MC3T3-E1 cells. The analysis of mRNA expression revealed a high expression of <i>Piezo1</i> and <i>Trpv4</i> in these cells. We also found that a PIEZO1 agonist, Yoda1, induced Ca<sup>2+</sup> response and activated cationic currents in these cells. Ca<sup>2+</sup> response was elicited when mechanical stimulation (MS), with shear stress, was induced by fluid flow in the MC3T3-E1 cells. Gene knockdown of <i>Piezo1</i> in the MC3T3-E1 cells, by transfection with siPiezo1, inhibited the Yoda1-induced response, but failed to inhibit the MS-induced response. When MC3T3-E1 cells were transfected with siTrpv4, the MS-induced response was abolished and Yoda1 response was attenuated. Moreover, the MS-induced response was inhibited by a TRPV4 antagonist HC-067047 (HC). Yoda1 response was also inhibited by HC in MC3T3-E1 cells and HEK cells, expressing both PIEZO1 and TRPV4. Meanwhile, the activation of PIEZO1 and TRPV4 reduced the proliferation of MC3T3-E1, which was reversed by knockdown of PIEZO1, and TRPV4, respectively. In conclusion, TRPV4 and PIEZO1 are distinct mechano-sensors in the MC3T3-E1 cells. However, PIEZO1 and TRPV4 modify the proliferation of these cells, implying that PIEZO1 and TRPV4 may be functional in the osteoblastic mechano-transduction. Notably, it is also found that Yoda1 can induce TRPV4-dependent Ca<sup>2+</sup> response, when both PIEZO1 and TRPV4 are highly expressed. |
| first_indexed | 2024-04-13T05:30:27Z |
| format | Article |
| id | doaj.art-a613adc2ced44e7f9e4a23684624ee48 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T05:30:27Z |
| publishDate | 2019-10-01 |
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| spelling | doaj.art-a613adc2ced44e7f9e4a23684624ee482022-12-22T03:00:28ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-10-012019496010.3390/ijms20194960ijms20194960PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-ProliferationMaki Yoneda0Hiroka Suzuki1Noriyuki Hatano2Sayumi Nakano3Yukiko Muraki4Ken Miyazawa5Shigemi Goto6Katsuhiko Muraki7Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanDepartment of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, JapanDepartment of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, JapanLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, JapanMechanical-loading and unloading can modify osteoblast functioning. Ca<sup>2+</sup> signaling is one of the earliest events in osteoblasts to induce a mechanical stimulus, thereby demonstrating the importance of the underlying mechanical sensors for the sensation. Here, we examined the mechano-sensitive channels PIEZO1 and TRPV4 were involved in the process of mechano-sensation in the osteoblastic MC3T3-E1 cells. The analysis of mRNA expression revealed a high expression of <i>Piezo1</i> and <i>Trpv4</i> in these cells. We also found that a PIEZO1 agonist, Yoda1, induced Ca<sup>2+</sup> response and activated cationic currents in these cells. Ca<sup>2+</sup> response was elicited when mechanical stimulation (MS), with shear stress, was induced by fluid flow in the MC3T3-E1 cells. Gene knockdown of <i>Piezo1</i> in the MC3T3-E1 cells, by transfection with siPiezo1, inhibited the Yoda1-induced response, but failed to inhibit the MS-induced response. When MC3T3-E1 cells were transfected with siTrpv4, the MS-induced response was abolished and Yoda1 response was attenuated. Moreover, the MS-induced response was inhibited by a TRPV4 antagonist HC-067047 (HC). Yoda1 response was also inhibited by HC in MC3T3-E1 cells and HEK cells, expressing both PIEZO1 and TRPV4. Meanwhile, the activation of PIEZO1 and TRPV4 reduced the proliferation of MC3T3-E1, which was reversed by knockdown of PIEZO1, and TRPV4, respectively. In conclusion, TRPV4 and PIEZO1 are distinct mechano-sensors in the MC3T3-E1 cells. However, PIEZO1 and TRPV4 modify the proliferation of these cells, implying that PIEZO1 and TRPV4 may be functional in the osteoblastic mechano-transduction. Notably, it is also found that Yoda1 can induce TRPV4-dependent Ca<sup>2+</sup> response, when both PIEZO1 and TRPV4 are highly expressed.https://www.mdpi.com/1422-0067/20/19/4960trpv4piezo1yoda1mc3t3-e1 cellsmechanical stimulationcell proliferation |
| spellingShingle | Maki Yoneda Hiroka Suzuki Noriyuki Hatano Sayumi Nakano Yukiko Muraki Ken Miyazawa Shigemi Goto Katsuhiko Muraki PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation International Journal of Molecular Sciences trpv4 piezo1 yoda1 mc3t3-e1 cells mechanical stimulation cell proliferation |
| title | PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation |
| title_full | PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation |
| title_fullStr | PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation |
| title_full_unstemmed | PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation |
| title_short | PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation |
| title_sort | piezo1 and trpv4 which are distinct mechano sensors in the osteoblastic mc3t3 e1 cells modify cell proliferation |
| topic | trpv4 piezo1 yoda1 mc3t3-e1 cells mechanical stimulation cell proliferation |
| url | https://www.mdpi.com/1422-0067/20/19/4960 |
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