Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation
), Leilei Zheng()Abstract
Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces (MFs) remain unclear. This study demonstrates that mechanosensitive ion channel Piezo1-mediated Ca2+ signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs under heavy-force conditions. Heavy MF up-regulated Piezo1 in PDLCs, reducing mitochondrial Ca2+ influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM.
Keywords
References
Chiu KH, Karpat M, Hahn J, et al. Cyclic stretching triggers cell orientation and extracellular matrix remodeling in a periodontal ligament 3D in vitro model. Adv Healthcare Mater. 2023;12(30):e2301422.
Yamaguchi M, Fukasawa S. Is inflammation a friend or foe for orthodontic treatment? Inflammation in orthodontically induced inflammatory root resorption and accelerating tooth movement. Int J Mol Sci. 2021;22(5):2388.
Li Y, Zhan Q, Bao M, Yi J, Li Y. Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade. Int J Oral Sci. 2021;13(1):20.
Gibson JM, King GJ, Keeling SD. Long-term orthodontic tooth movement response to short-term force in the rat. Angle Orthod. 1992;62(3):211–215. discussion 216.
Murphy CA, Chandhoke T, Kalajzic Z, et al. Effect of corticision and different force magnitudes on orthodontic tooth movement in a rat model. Am J Orthod Dentofacial Orthop. 2014;146(1):55–66.
Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330(6000):55–60.
Du G, Li L, Zhang X, et al. Roles of TRPV4 and piezo channels in stretch-evoked Ca2+ response in chondrocytes. Exp Biol Med. 2020;245(3):180–189.
Jiang Y, Guan Y, Lan Y, et al. Mechanosensitive Piezo1 in periodontal ligament cells promotes alveolar bone remodeling during orthodontic tooth movement. Front Physiol. 2021;12:767136.
Lukacs L, Rennekampff I, Tenenhaus M, Rennekampff HO. The periodontal ligament, temperature-sensitive ion channels TRPV1-4, and the mechanosensitive ion channels Piezo1 and 2: a Nobel connection. J Periodontal Res. 2023;58(4):687–696.
Atcha H, Jairaman A, Holt JR, et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat Commun. 2021;12(1):3256.
Dombroski JA, Hope JM, Sarna NS, King MR. Channeling the force: piezo1 mechanotransduction in cancer metastasis. Cells. 2021;10(11):2815.
Li J, Qi F, Su H, et al. GRP75-faciliated mitochondria-associated ER membrane (MAM) integrity controls cisplatin-resistance in ovarian cancer patients. Int J Biol Sci. 2022;18(7):2914–2931.
Garbincius JF, Elrod JW. Mitochondrial calcium exchange in physiology and disease. Physiol Rev. 2022;102(2):893–992.
Missiroli S, Patergnani S, Caroccia N, et al. Mitochondria-associated membranes (MAMs) and inflammation. Cell Death Dis. 2018;9(3):329.
Li F, Li G, Hu H, Liu R, Chen J, Zou S. Effect of parathyroid hormone on experimental tooth movement in rats. Am J Orthod Dentofacial Orthop. 2013;144(4):523–532.
Nakano T, Hotokezaka H, Hashimoto M, et al. Effects of different types of tooth movement and force magnitudes on the amount of tooth movement and root resorption in rats. Angle Orthod. 2014;84(6):1079–1085.
Kanzaki H, Chiba M, Shimizu Y, Mitani H. Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res. 2002;17(2):210–220.
Xie Y, Tang Q, Yu S, et al. Orthodontic force-induced BMAL1 in PDLCs is a vital osteoclastic activator. J Dent Res. 2022;101(2):177–186.
Hlaing EEH, Ishihara Y, Wang Z, Odagaki N, Kamioka H. Role of intracellular Ca2+-based mechanotransduction of human periodontal ligament fibroblasts. Faseb J. 2019;33(9):10409–10424.
Odagaki N, Ishihara Y, Wang Z, et al. Role of osteocyte-PDL crosstalk in tooth movement via SOST/sclerostin. J Dent Res. 2018;97(12):1374–1382.
Wang H, Li T, Jiang Y, et al. Force-loaded cementocytes regulate osteoclastogenesis via S1P/S1PR1/Rac1 axis. J Dent Res. 2023;102(12):1376–1386.
Marchiano F, Haering M, Habermann BH. The mitoXplorer 2.0 update: integrating and interpreting mitochondrial expression dynamics within a cellular context. Nucleic Acids Res. 2022;50(W1):W490–W499.
Mohana Devi S, Abishek Kumar B, Mahalaxmi I, Balachandar V. Leber’s hereditary optic neuropathy: current approaches and future perspectives on Mesenchymal stem cell-mediated rescue. Mitochondrion. 2021;60:201–218.
Zhang D, Lin W, Jiang S, et al. Lepr-expressing PDLSCs contribute to periodontal homeostasis and respond to mechanical force by Piezo1. Adv Sci. 2023;10(29):e2303291.
Du Y, Yang K. Role of mechanosensitive ion channel Piezo1 in tension-side orthodontic alveolar bone remodeling in rats. Arch Oral Biol. 2023;155:105798.
Wang L, You X, Lotinun S, Zhang L, Wu N, Zou W. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk. Nat Commun. 2020;11(1):282.
Solis AG, Bielecki P, Steach HR, et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature. 2019;573(7772):69–74.
Jiang F, Yin K, Wu K, et al. The mechanosensitive Piezo 1 channel mediates heart mechano-chemo transduction. Nat Commun. 2021;12(1):869.
Gudipaty SA, Lindblom J, Loftus PD, et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017;543(7643):118–121.
Syeda R, Florendo MN, Cox CD, et al. Piezo1 channels are inherently mechanosensitive. Cell Rep. 2016;17(7):1739–1746.
Marchi S, Patergnani S, Missiroli S, et al. Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death. Cell Calcium. 2018;69:62–72.
Szymański J, Janikiewicz J, Michalska B, et al. Interaction of mitochondria with the endoplasmic reticulum and plasma membrane in calcium homeostasis, lipid trafficking and mitochondrial structure. Int J Mol Sci. 2017;18(7):1576.
Agyapong ED, Pedriali G, Ramaccini D, et al. Calcium signaling from sarcoplasmic reticulum and mitochondria contact sites in acute myocardial infarction. J Transl Med. 2024;22(1):552.
Mao H, Chen W, Chen L, Li L. Potential role of mitochondria-associated endoplasmic reticulum membrane proteins in diseases. Biochem Pharmacol. 2022;199:115011.
Xue Y, Morris JL, Yang K, et al. SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria. Nat Commun. 2021;12(1):5404.
Zhang D, Wang F, Li P, Gao Y. Mitochondrial Ca2+ homeostasis: emerging roles and clinical significance in cardiac remodeling. Int J Mol Sci. 2022;23(6):3025.
Quan Y, Xin Y, Tian G, Zhou J, Liu X. Mitochondrial ROS-modulated mtDNA: a potential target for cardiac aging. Oxid Med Cell Longev. 2020;2020:9423593.
Xian H, Karin M. Oxidized mitochondrial DNA: a protective signal gone awry. Trends Immunol. 2023;44(3):188–200.
Xian H, Watari K, Sanchez-Lopez E, et al. Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling. Immunity. 2022;55(8):1370–1385.e8.
Liu Z, Wang M, Wang X, et al. XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA-cGAS-STING signaling in macrophages during acute liver injury. Redox Biol. 2022;52:102305.
Chung KW, Dhillon P, Huang S, et al. Mitochondrial damage and activation of the STING pathway lead to renal inflammation and fibrosis. Cell Metabol. 2019;30(4):784–799.e5.
Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol. 2020;15:235–259.
京公网安备11010802044758号