Highlights
- •Nervous system participates in the orthodontic tooth movement process and regulating bone remodeling as well as periodontal ligament metabolism via different pathways.
- •Sensory neural markers, such as calcitonin gene-related peptide and substance P, are involved in the neurovascular reaction to orthodontic forces in the periodontium.
- •Sympathetic nervous system can enhance tooth movement by upregulating the expression of various receptors and pathways promoting osteoclastogenesis.
- •Leptin can not only modulate the inflammatory response of immune cells to mechanical force but also have a significant impact on periodontal ligament cell apoptosis during orthodontic tooth movement.
ABSTRACT
With increased understanding of orthodontic tooth movement (OTM) in recent years,
neural regulation of OTM has become an emerging and expanding area of research. Numerous
studies have shown that the nervous system, including the central and peripheral systems,
regulates bone remodeling through various neuropeptides, receptor expression, etc.
OTM is a unique periodontal tissue remodeling process induced by mechanical force,
including changes in the periodontal ligament metabolism and alveolar bone remodeling.
Various studies have shown that the nervous system participates in the OTM process
and regulates the periodontal ligament metabolism. This review summarizes the current
researches on neural regulation of bone remodeling and the biological responses within
the periodontal ligamentduring OTM under therapeutic loading. We also discuss the
issues that remain to be addressed in this field. The exploration of neural regulation
on OTM not only assists us to understand the mechanism of OTM more thoroughly, but
also provides a new insight to accelerate tooth movement in the future.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the World Federation of OrthodontistsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Neural regulation of bone remodeling: identifying novel neural molecules and pathways between brain and bone.J Cell Physiol. 2019; 234: 5466-5477
- Neuromodulation of bone: role of different peptides and their interactions (review).Mol Med Rep. 2021; 23: 1
- Force-induced Adrb2 in periodontal ligament cells promotes tooth movement.J Dent Res. 2014; 93: 1163-1169
- Suppression of tooth movement-induced sclerostin expression using β-adrenergic receptor blockers.Oral Dis. 2020; 26: 621-629
- Sympathetic nervous system contributes to orthodontic tooth movement by central neural regulation from hypothalamus.Histol Histopathol. 2020; 35: 1493-1502
- Orthodontic tooth movement-activated sensory neurons contribute to enhancing osteoclast activity and tooth movement through sympathetic nervous signalling.Eur J Orthod. 2022; 44: 404-411
- Neuronal control of bone remodeling.Toxicol Pathol. 2017; 45: 894-903
- Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur.Neuroscience. 2002; 113: 155-166
- Deficiency of α calcitonin-gene-related peptide impairs peri-implant angiogenesis and osseointegration via suppressive vasodilative activity.Biochem Biophys Res Commun. 2018; 498: 139-145
- Absence of substance P and the sympathetic nervous system impact on bone structure and chondrocyte differentiation in an adult model of endochondral ossification.Matrix Biol. 2014; 38: 22-35
- Substance P stimulates bone marrow stromal cell osteogenic activity, osteoclast differentiation, and resorption activity in vitro.Bone. 2009; 45: 309-320
- Substance P upregulates osteoclastogenesis by activating nuclear factor kappa B in osteoclast precursors.Acta Otolaryngol. 2005; 125: 130-133
- Biology of bone tissue: structure, function, and factors that influence bone cells.BioMed Res Int. 2015; 2015421746
- Innervation of the tibial epiphysis through the intercondylar foramen.Bone. 2019; 120: 297-304
- Crosstalk between neuropeptides SP and CGRP in regulation of BMP2-induced bone differentiation.Connect Tissue Res. 2018; 59: 81-90
- Calcitonin gene-related peptide regulates mitogen-activated protein kinase pathway to decrease transforming growth factor β1-induced hepatic plasminogen activator inhibitor-1 mRNA expression in HepG2 cells.Biosci Biotechnol Biochem. 2014; 78: 787-790
- Leptin regulates bone formation via the sympathetic nervous system.Cell. 2002; 111: 305-317
- Leptin regulation of bone resorption by the sympathetic nervous system and CART.Nature. 2005; 434: 514-520
- Hypothalamic control of bone metabolism.Best Pract Res Clin Endocrinol Metab. 2014; 28: 713-723
- Central depletion of brain-derived neurotrophic factor in mice results in high bone mass and metabolic phenotype.Endocrinology. 2012; 153: 5394-5405
- Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress.Int J Oral Sci. 2022; 14: 39
- Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating beta2-adrenergic receptors.Bone. 1998; 22: 471-478
- Deletion of β-adrenergic receptor 1, 2, or both leads to different bone phenotypes and response to mechanical stimulation.J Bone Miner Res. 2012; 27: 1252-1262
- Neuronal signaling and the regulation of bone remodeling.Cell Mol Life Sci. 2005; 62: 2339-2349
- Central autonomic control of the bone marrow: multisynaptic tract tracing by recombinant pseudorabies virus.Neuroscience. 2005; 134: 947-963
- Leptin effect on RANKL and OPG expression in MC3T3-E1 osteoblasts.J Cell Biochem. 2006; 98: 1123-1129
- Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass.Cell. 2000; 100: 197-207
- Peripheral leptin regulates bone formation.J Bone Miner Res. 2013; 28: 22-34
- Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus.J Neuroendocrinol. 1996; 8: 733-735
- Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways.J Bone Miner Res. 2006; 21: 1600-1607
- Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice.J Bone Miner Res. 2005; 20: 994-1001
- Compensatory changes in [125I]-PYY binding in Y receptor knockout mice suggest the potential existence of further Y receptor(s).Neuropeptides. 2005; 39: 21-28
- Hypothalamic Y2 receptors regulate bone formation.J Clin Invest. 2002; 109: 915-921
- Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity.Obesity (Silver Spring). 2011; 19: 2137-2148
- Regional distribution of Y-receptor subtype mRNAs in rat brain.Eur J Neurosci. 1999; 11: 1431-1448
- Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis.J Biol Chem. 2007; 282: 19092-19102
- Osteoblast specific Y1 receptor deletion enhances bone mass.Bone. 2011; 48: 461-467
- NPY signalling in early osteoblasts controls glucose homeostasis.Mol Metab. 2015; 4: 164-174
- Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.PLOS ONE. 2009; 4: e8415
- Interaction between Schwann cells and osteoblasts in vitro.Int J Oral Sci. 2010; 2: 74-81
- Skeletal stem cell-Schwann cell circuitry in mandibular repair.Cell Rep. 2019; 28 (e5): 2757-2766
- Possible function of GDNF and Schwann cells in wound healing of periodontal tissue.J Periodontal Res. 2020; 55: 830-839
- Cellular, molecular, and tissue-level reactions to orthodontic force.Am J Orthod Dentofacial Orthop. 2006; 129 (e1–32): 469
- The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt.Eur J Orthod. 2006; 28: 221-240
- Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans.Eur J Oral Sci. 2007; 115: 355-362
- M1-like macrophage polarization promotes orthodontic tooth movement.J Dent Res. 2015; 94: 1286-1294
- T cells are required for orthodontic tooth movement.J Dent Res. 2015; 94: 1463-1470
- Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade.Int J Oral Sci. 2021; 13: 20
- Orthodontic pain: from causes to management-a review.Eur J Orthod. 2007; 29: 170-179
- Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement.Am J Orthod Dentofacial Orthop. 2006; 130: 364-370
- Inferior alveolar nerve transection inhibits increase in osteoclast appearance during experimental tooth movement.Bone. 2000; 26: 663-669
- Effect of surgical denervation on orthodontic tooth movement in rats.Am J Orthod Dentofacial Orthop. 2007; 131: 620-626
- Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats.Neuropeptides. 2015; 52: 31-37
- Heme oxygenase-1 protects human periodontal ligament cells against substance P-induced RANKL expression.J Periodontal Res. 2010; 45: 367-374
- Effect of systemic delivery of substance P on experimental tooth movement in rats.Am J Orthod Dentofacial Orthop. 2019; 155: 642-649
- Selective β2-adrenergic Antagonist butoxamine Reduces Orthodontic Tooth Movement.J Dent Res. 2014; 93: 807-812
- Experimental tooth movement-induced osteoclast activation is regulated by sympathetic signaling.Bone. 2013; 52: 39-47
- Salivary leptin levels in normal weight and overweight individuals and their correlation with orthodontic tooth movement.Angle Orthod. 2017; 87: 739-744
- Obesity attenuates force-induced tooth movement in mice with the elevation of leptin level: a preliminary translational study.Am J Transl Res. 2018; 10: 4107-4118
- Effects of the multifunctional hormone leptin on orthodontic tooth movement in rats.Am J Transl Res. 2020; 12: 1976-1984
- Evaluation of leptin concentration in gingival crevicular fluid (GCF) during orthodontic tooth movement and its correlation to the rate of tooth movement.J Orthod Sci. 2019; 8: 6
- Tooth movement, orofacial pain, and leptin, interleukin-1β, and tumor necrosis factor-α levels in obese adolescents.Angle Orthod. 2022; 92: 95-100
- Leptin reduces in vitro cementoblast mineralization and survival as well as induces PGE2 release by ERK1/2 commitment.Clin Oral Investig. 2021; 25: 1933-1944
- Orthodontic tooth movement: the biology and clinical implications.Kaohsiung J Med Sci. 2018; 34: 207-214
- 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
- Substance P immunoreactivity in periodontal tissues during orthodontic tooth movement.Bone Miner. 1990; 11: 19-29
- Expression of neuropeptides (CGRP, substance P) during and after orthodontic tooth movement in the rat.Eur J Orthod. 1995; 17: 311-325
- Microanatomical changes and biomolecular expression at the PDL-entheses during experimental tooth movement.J Periodontal Res. 2019; 54: 251-258
- On a path to unfolding the biological mechanisms of orthodontic tooth movement.J Dent Res. 2009; 88: 597-608
- Neuropeptides stimulate production of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in human dental pulp cells.Inflamm Res. 2004; 53: 199-204
- Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells.Clin Exp Immunol. 2007; 150: 567-575
- Composition changes in gingival crevicular fluid during orthodontic tooth movement: comparisons between tension and compression sides.Eur J Oral Sci. 2006; 114: 416-422
- Upregulated leptin in periodontitis promotes inflammatory cytokine expression in periodontal ligament cells.J Periodontol. 2015; 86: 917-926
- Impact of leptin on periodontal ligament fibroblasts during mechanical strain.Int J Mol Sci. 2021; 22
- Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations.J Periodontol. 2007; 78: 453-458
- Leptin attenuates hypoxia-induced apoptosis in human periodontal ligament cells via the reactive oxygen species-hypoxia-inducible factor-1α pathway.Exp Physiol. 2021; 106: 1752-1761
- Leptin in dental pulp and periapical tissues: a narrative review.Int J Mol Sci. 2022; 23: 1984
Article info
Publication history
Published online: September 26, 2022
Accepted:
August 25,
2022
Received:
August 24,
2022
Footnotes
Funding: This work was financially supported by the National Natural Science Foundations of China number 62076011 (Dr. Zhou), number 81970909 (Dr. Liu), and number 82170996 (Dr. He); Key Research and Development Plan of Ningxia Hui Autonomous Region (No.2020BCG01001); National multidisciplinary cooperative diagnosis and treatment capacity building project of Peking University School of Stomatology (PKUSSNMP202020); New Clinical Technology Fund of Peking University School of Stomatology (PKUSSNCT-20A07); and China Oral Health Foundation (A2021057).
Competing interests: Authors have completed and submitted the ICMJE Form for Disclosure of potential conflicts of interest. None declared.
Provenance and peer review: Non-commisioned, internally peer reviewed
Identification
Copyright
© 2022 World Federation of Orthodontists. Published by Elsevier Inc. All rights reserved.
