A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement

Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal gui...

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Main Authors: Sinan Şen, Christopher J. Lux, Ralf Erber
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/15/8297
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author Sinan Şen
Christopher J. Lux
Ralf Erber
author_facet Sinan Şen
Christopher J. Lux
Ralf Erber
author_sort Sinan Şen
collection DOAJ
description Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the regulation of bone remodeling. Amongst them, Semaphorin 3A is particular interesting as it concurrently induces osteoblast differentiation and disturbs osteoclast differentiation. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). The association of the transcription factor Osterix (SP7) and SEMA3A was studied by RT-qPCR. Mechanisms involved in SEMA3A-mediated osteoblast differentiation were assessed by Rac1GTPase pull-downs, β-catenin expression analyses (RT-qPCR) and nuclear translocation assays (IF). Osteogenic markers were analyzed by RT-qPCR. Results: SEMA3A, PLXNA1 and NRP1 were differentially regulated by tension or compressive forces in hPDLF. Osterix (SP7) displayed the same pattern of regulation. Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Conclusion: Sema3A, its receptors and Osterix are regulated by mechanical forces in hPDLF. SEMA3A upregulation was associated with Osterix (SP7) modulation. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Thus, Semaphorin 3A might contribute to bone remodeling during induced tooth movement.
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spelling doaj.art-75e141d9eb8b49ce9c575c7093f45b302023-11-22T05:46:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012215829710.3390/ijms22158297A Potential Role of Semaphorin 3A during Orthodontic Tooth MovementSinan Şen0Christopher J. Lux1Ralf Erber2Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, GermanyDepartment of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, GermanyDepartment of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, GermanyBackground: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the regulation of bone remodeling. Amongst them, Semaphorin 3A is particular interesting as it concurrently induces osteoblast differentiation and disturbs osteoclast differentiation. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). The association of the transcription factor Osterix (SP7) and SEMA3A was studied by RT-qPCR. Mechanisms involved in SEMA3A-mediated osteoblast differentiation were assessed by Rac1GTPase pull-downs, β-catenin expression analyses (RT-qPCR) and nuclear translocation assays (IF). Osteogenic markers were analyzed by RT-qPCR. Results: SEMA3A, PLXNA1 and NRP1 were differentially regulated by tension or compressive forces in hPDLF. Osterix (SP7) displayed the same pattern of regulation. Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Conclusion: Sema3A, its receptors and Osterix are regulated by mechanical forces in hPDLF. SEMA3A upregulation was associated with Osterix (SP7) modulation. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Thus, Semaphorin 3A might contribute to bone remodeling during induced tooth movement.https://www.mdpi.com/1422-0067/22/15/8297tooth movementmechanotransductionneuronal guidance moleculesSemaphorinsbone remodeling
spellingShingle Sinan Şen
Christopher J. Lux
Ralf Erber
A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
International Journal of Molecular Sciences
tooth movement
mechanotransduction
neuronal guidance molecules
Semaphorins
bone remodeling
title A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
title_full A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
title_fullStr A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
title_full_unstemmed A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
title_short A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
title_sort potential role of semaphorin 3a during orthodontic tooth movement
topic tooth movement
mechanotransduction
neuronal guidance molecules
Semaphorins
bone remodeling
url https://www.mdpi.com/1422-0067/22/15/8297
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