Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.