BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or to...BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.展开更多
The brain serves as the core component of the central nervous system and plays a pivotal role in regulating the functions of various essential organs throughout the body.The skeletal system serves as the fundamental s...The brain serves as the core component of the central nervous system and plays a pivotal role in regulating the functions of various essential organs throughout the body.The skeletal system serves as the fundamental supportive and protective framework of the human body and is extensively innervated by nerves.Currently,a large body of epidemiological and experimental evidence confirms the close interplay between bones and the brain,but the underlying mechanisms remain unclear.This review is anchored on the concept of the brain-bone axis,aiming to gain a deeper understanding of the physiological and pathological interactions between these two organs.A comprehensive analysis of the potential foundations and mechanisms underlying the intricate association between the brain and the skeleton is offered.In summary,the brain can influence skeletal homeostasis through modulation of the neuromolecules,extracellular vesicles,and brain-marrow neural circuit;conversely,the skeleton can influence the brain in its development,function,and pathology by physical exercise,massage therapy,and skeletal trauma.Simultaneously,the strategies for the treatment of skeletal and neurological disorders were organized,in which Traditional Chinese Medicine appears to offer new perspectives for the prevention and disease management,ultimately aiming to furnish patients with more effective therapeutic methods.展开更多
Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorate...Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorates stroke outcomes.Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.Methods Patients with AIS and healthy individuals were enrolled in the study.Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC(BM-MSC)right after reperfusion.Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin.Thickness of mucus was assessed with Alcian blue staining.Hepatic glucocorticoid(GC)metabolism was analysed with expression of HSD11B2,HSD11B1 and SRD5A1.Results We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation.The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia.Transferred-BM MSC restored the mucus thickness,thus preserving gut microbiota homeostasis and preventing enterobacterial invasion.Mechanistically,the transferred-BM MSC stationed in the liver and enhanced peroxisome proliferator-activated receptorγsignalling in hepatocytes.Consequently,expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.Conclusions Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut brain axis in AIS.展开更多
基金Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2022YFA1105800the National Natural Science Foundation of China,No.81970940.
文摘BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.
基金supported by the National Natural Science Foundation of China(82374615)the Major Science and Technology Innovation Project of Shandong Province(2022CXGC020510 and 2024CXGC010609)+4 种基金the Natural Science Foundation of Shandong Province(ZR2024MH189)the University Youth Innovation Team of Shandong Province(2023KJ176)Shandong Province Traditional Chinese Medicine Science and Technology project(M-2022253)Shandong Provincial Medical and Health Science and Technology Project(202412040294)the clinical-basic joint innovation team project of Shandong First Medical University(CX202408)。
文摘The brain serves as the core component of the central nervous system and plays a pivotal role in regulating the functions of various essential organs throughout the body.The skeletal system serves as the fundamental supportive and protective framework of the human body and is extensively innervated by nerves.Currently,a large body of epidemiological and experimental evidence confirms the close interplay between bones and the brain,but the underlying mechanisms remain unclear.This review is anchored on the concept of the brain-bone axis,aiming to gain a deeper understanding of the physiological and pathological interactions between these two organs.A comprehensive analysis of the potential foundations and mechanisms underlying the intricate association between the brain and the skeleton is offered.In summary,the brain can influence skeletal homeostasis through modulation of the neuromolecules,extracellular vesicles,and brain-marrow neural circuit;conversely,the skeleton can influence the brain in its development,function,and pathology by physical exercise,massage therapy,and skeletal trauma.Simultaneously,the strategies for the treatment of skeletal and neurological disorders were organized,in which Traditional Chinese Medicine appears to offer new perspectives for the prevention and disease management,ultimately aiming to furnish patients with more effective therapeutic methods.
基金supported by Guangzhou Key Research Program on Brain Science(202206060001 to ZL)Guangdong Basic and Applied Basic Research Foundation(2020A1515010056 to BZ)+3 种基金National Natural Science Foundation of China(82171307 to ZL)National Natural Science Foundation of China(82271348 to WC)Fundamental Research Funds for the Central Universities(23ykbj006 to WC)Science and Technology Program of Guangzhou(2023B01J1002 to ZL).
文摘Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorates stroke outcomes.Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.Methods Patients with AIS and healthy individuals were enrolled in the study.Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC(BM-MSC)right after reperfusion.Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin.Thickness of mucus was assessed with Alcian blue staining.Hepatic glucocorticoid(GC)metabolism was analysed with expression of HSD11B2,HSD11B1 and SRD5A1.Results We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation.The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia.Transferred-BM MSC restored the mucus thickness,thus preserving gut microbiota homeostasis and preventing enterobacterial invasion.Mechanistically,the transferred-BM MSC stationed in the liver and enhanced peroxisome proliferator-activated receptorγsignalling in hepatocytes.Consequently,expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.Conclusions Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut brain axis in AIS.
