Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis

Ying, Lin; Xing, Qu; Qin, Wei; Melo, Mary Anne S.; Zou, Rui; Xu, Meng; Zhang, Xiaolei; Xu, Hockin H.K.; Zhao, Lin

doi:10.1155/2017/8724503

Cited by 36 publications

(8 citation statements)

References 26 publications

(32 reference statements)

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“…A recent study has found that the expression of SEMA3A and its receptor NRP-1 decreased in a time-dependent manner in mechanical stress-stimulated chondrocytes, and that overexpressing SEMA3A could reduce mechanical stress-induced release of inflammatory cytokines in those chondrocytes [ 20 ]. Moreover, a decline in the expression of SEMA3A/NRP-1 signaling has been reported earlier in rats with periapical lesions as well as patients with apical periodontitis [ 31 ]. Our preliminary investigation found that SEMA3A also had a meaningful expression in LPS-challenged chondrocytes, as its expression decreased with the increase in the duration of LPS stimulation.…”

Section: Discussionmentioning

confidence: 75%

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Zhang

Lü

et al. 2021

Bioengineered

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Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.

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Section: Discussionmentioning

confidence: 75%

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Zhang

Lü

et al. 2021

Bioengineered

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“…The role of Sema3A in the regulation of bone remodeling is increasingly recognized [ 36 ] and also includes functions in the periodontium. Lin et al found a reduced expression of Sema3A and Nrp1 in apical periodontitis, which suggests an involvement of Sema3A-dependent signaling in periapical bone resorption [ 37 ]. Using the physiological initiation of bone remodeling in the rat mandible as a model, Hassan et al observed that a temporary loss of Sema3A expression was associated with the migration and activation of osteoclast precursor cells [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement

Şen

Lux

Erber

2021

IJMS

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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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“…In previous study, Sema3A promoted osteoblast differentiation by binding to NRP‐1‐plexin‐A1 receptor complex 26 . A recent study has shown that the expression of Sema3A/ Nrp‐1 significantly decreased in periapical periodontitis patients and rat models of periapical periodontitis, suggesting that Sema3A/Nrp‐1 may contribute to the pathological development of apical periodontitis 27 . In addition, Sema3A‐positive cells were observed in both the dental follicles of developing tooth germs and mature PDL tissue 28 .…”

Section: Introductionmentioning

confidence: 88%

Semaphorin 3A attenuates the hypoxia suppression of osteogenesis in periodontal ligament stem cells

Chang

Zhou

et al. 2022

J of Periodontal Research

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Objective and Background The occurrence and development of periodontitis are closely related to hypoxia of the periodontal microenvironment. Periodontal ligament stem cells (PDLSCs) are considered to have potential to regenerate periodontal tissues. Semaphorin 3A (Sema3A) plays an essential role in promoting osteogenesis. However, the effect of Sema3A on osteogenesis of PDLSCs under hypoxia remains unclear. The aim of this study was to investigate the effect of Sema3A on osteogenesis of PDLSCs under hypoxia. Methods Isolated PDLSCs were identified using flow cytometry. Adipogenic differentiation potential was identified by oil red O staining. Osteogenesis was measured using Alizarin Red S staining and ALP staining. Intracellular hypoxia was induced using cobalt chloride (CoCl2). The expression level of hypoxia‐inducible factor‐1α (HIF‐1α) was detected via ELISA. Expression of osteogenic markers and Sema3A was analyzed using western blot and real‐time PCR. Results The proliferation and osteogenesis of PDLSCs were markedly inhibited with increased concentrations of CoCl2. Under the treatment with a low concentration of CoCl2, expression of related osteogenic markers and Sema3A decreased in a time‐dependent manner. ARS and ALP staining results also showed that osteogenic calcification decreased under hypoxia. Apigenin, an inhibitor of HIF‐1α, effectively up‐regulated expression of Sema3A and osteogenic markers with CoCl2 treatment. Moreover, exogenous Sema3A significantly increased the expression of osteogenesis‐related markers and mineralization of PDLSCs according to ALP and ARS staining with CoCl2 treatment. Conclusions Hypoxia markedly inhibited osteogenesis of PDLSCs. Sema3A explicitly attenuated the hypoxia suppression of osteogenesis in PDLSCs.

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Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis

Cited by 36 publications

References 26 publications

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement

Semaphorin 3A attenuates the hypoxia suppression of osteogenesis in periodontal ligament stem cells

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