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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MDPI AG
2021-08-01
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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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