Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 Aug 2;22(15):8297. doi: 10.3390/ijms22158297.
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.
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.
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.
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.
正畸治疗过程中的牙齿诱导移动需要机械诱导的骨重塑。除了各种细胞因子和生长因子外，神经导向分子因其在骨稳态中的作用而受到关注，因此在牙齿移动过程中可能具有潜在作用。几种神经导向分子已被牵涉到骨重塑的调节中。其中，Semaphorin 3A 特别有趣，因为它同时诱导成骨细胞分化并干扰破骨细胞分化。
通过对原代人牙周成纤维细胞（hPDLF）和牙槽骨成骨细胞（hOB）施加压缩力和张力，评估 Sema3A 及其受体 PlexinA1 和 Neuropilin 的机械调节（RT-qPCR、WB）。通过 RT-qPCR 研究转录因子 Osterix（SP7）和 SEMA3A 的关联。通过 Rac1GTPase 下拉、β-连环蛋白表达分析（RT-qPCR）和核转位测定（IF）评估 SEMA3A 介导的成骨细胞分化的机制。通过 RT-qPCR 分析成骨标志物。
Sema3A、PLXNA1 和 NRP1 在 hPDLF 中受张力或压缩力的差异调节。Osterix（SP7）显示出相同的调节模式。重组 Sema3A 诱导 Rac1GTPase 的激活、β-连环蛋白的核转位和成骨标记基因的表达。
Sema3A、其受体和 Osterix 受 hPDLF 中的机械力调节。Sema3A 的上调与 Osterix（SP7）的调节相关。Sema3A 增强 hOB 中成骨标记基因的表达可能依赖于涉及 Rac1GTPase 和 β-连环蛋白的途径。因此，Semaphorin 3A 可能有助于诱导牙齿移动过程中的骨重塑。
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