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Objective To explore the effect of cannabinoid receptor 2(CB2)on orthodontic tooth movement(OTM)rate and periodontal tissue reconstruction of pressure area in mice.Methods Thirty CB2-/-male mice and thirty littermate control WT male mice were individually accepted the orthodontic appliance at their age of 6 weeks.The mice were respectively scarified at 3 days,7 days,14 days and 21 days after the operation.Then the tooth movement distance was examined through the stereomicroscope.Hematoxylin-eosin staining was performed to explore the biological responses of periodontium at the distal mesial root pressure area.Anti-tartrate acid phospha-tase staining was performed to calculate the number and distribution of osteoclasts at the distal mesial root pressure area,and MMP-9 was evaluated by immunohistochemistry to examine the number of MMP-9(+)monocytes and multinucleated cells in the same district as the TRAP staining.Results Compared with those WT mice at 3,7,14 and 21 days,OTM distance showed a gradual increased tendency according with experimental time over 21 days.The widths of periodontal ligament on the pressure side were markedly greater in CB2-/-mice than WT mice at 7,14 and 21 days(P＜0.000 1).The numbers of TRAP positive osteoclasts were significantly greater in CB2-/-mice than those in WT mice at 14 days of OTM(P＜0.001).MMP-9 immunohistochemical staining showed that the number of MMP-9(+)monocytes and multinucleated cells was more in CB2-/-mice than that in WT mice at 14 days of OTM(P＜0.05).Conclusion The absence of CB2 accelerates orthodontic tooth movement under or-thodontic force.The absence of CB2 reinforces bone resorption in orthodontic tooth movement compressive area dur-ing orthodontic tooth movement.
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BACKGROUND:Recent studies have shown that the Notch signaling pathway plays a varying role in osteoporosis,and in-depth research in this field is of great significance to the prevention and treatment of osteoporosis.Traditional Chinese medicine has become the focus of research in today's society due to its obvious multi-faceted,multi-level benefits in alleviating osteoporosis with less adverse effects. OBJECTIVE:To analyze and summarize domestic and international literature to further understand the connection between the Notch signaling pathway and osteoporosis and to elucidate the mechanism by which traditional Chinese medicine prevents and treats osteoporosis via the Notch signaling pathway. METHODS:CNKI,WanFang,and VIP were searched with the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathway,traditional Chinese medicine,pill,experiment"in Chinese.PubMed,Nature,and Embase were retrieved using the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,mesenchymal stem cells,signal pathway,traditional Chinese medicine,pill,experiment"in English.The search time was from database inception to October 2022. RESULTS AND CONCLUSION:The Notch signaling pathway plays a role in the development and progression of osteoporosis to varying degrees by regulating the differentiation and proliferation of mesenchymal stem cells,osteoblasts and osteoclasts.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,osteoblasts and osteoclasts by directly or indirectly regulating key cytokines such as Notch1,Jagged1,Hes,Hey,macrophage colony-stimulating factor and nuclear factor-κB receptor-activating factor ligand,which in turn promotes or inhibits bone formation and ultimately has a certain effect on the prevention and treatment of osteoporosis.The active ingredients of Chinese herbs are mostly extracted from herbs for kidney tonifying,such as Epimedium,Cortex Eucommiae,Malaytea Scurfpea Fruit,Eleutherococcus Senticosus,Ligustrum Lucidum.Moreover,herbal compounds and preparations have the effect of tonifying kidney and strengthening bone,which provides more herbal options and directions for the subsequent study of Notch signaling pathway toward the prevention and treatment of osteoporosis.Current studies on traditional Chinese medicine mainly focus on active ingredients and single herbal extracts,with relatively few clinical trials on Chinese herbal compounds and preparations.Fewer studies have been conducted on the regulation of Notch signaling pathways by acupuncture,manipulation,and integrated Chinese and Western medicine to prevent and treat osteoporosis.Therefore,there is a need to explore the mechanisms by which traditional Chinese medicine technology-based therapies and integrated Chinese and Western medicine regulate the Notch signaling pathway to treat osteoporosis.
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BACKGROUND:It has been demonstrated that osteoclast activation plays an important role in skeletal system-related diseases.The mechanism of regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA has not been fully elucidated. OBJECTIVE:To review and summarize relevant literature in and outside China,and to review the regulation of osteoclast activation by different non-coding RNAs in extracellular vesicles in different diseases,so as to provide a certain direction for subsequent research. METHODS:"Non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclasts,extracellular vesicles,exosome,microparticle,apoptotic bodies"were used as search terms to search the databases of CNKI,WanFang,and VIP."Extracellular vesicles,exosome,microparticle,apoptotic bodies,non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclast"were used as search terms to search PubMed.Finally,71 articles were included. RESULTS AND CONCLUSION:(1)The activation of osteoclasts is affected by many factors,among which the specific mechanism of non-coding RNA regulating osteoclast activation is not clear.(2)Extracellular vesicles can be secreted by osteoblasts,bone marrow mesenchymal stem cells,tumor cells and other cells.As a carrier of intercellular communication,extracellular vesicles can carry non-coding RNA to regulate osteoclast activation.(3)In the current studies on the regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA,most of the diseases are osteoporosis,followed by tumor bone metastasis,and most types of non-coding RNA are miRNA.(4)There are relatively few studies on the regulation of extracellular vesicles carrying lncRNA and circRNA and snoRNA on osteoclast activation,and the regulatory mechanism is mainly ceRNA mechanism.(5)In conclusion,an in-depth study of the regulatory mechanism of extracellular vesicles carrying non-coding RNA on osteoclast activation is helpful to find key targets for the treatment of skeletal system-related diseases.
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BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.
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BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.
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BACKGROUND:Tabersonine has shown good therapeutic effects in diseases such as myocardial remodeling,acute kidney injury and lung injury due to its anti-inflammatory biological activity.Prosthetic wear particles often lead to aseptic inflammation,and the massive release of inflammatory factors further promotes periprosthetic bone destruction and bone loss;however,there are no basic studies on the efficacy of tabersonine on periprosthetic osteolysis. OBJECTIVE:To investigate the effects of tabersonine on osteoclast activation,expression of inflammatory factors and inflammatory osteolysis induced by wear particles. METHODS:(1)Cell experiment:RAW264.7 cells were divided into four groups for culture.A complete medium was added in the control group.Osteoclast induction medium(50 ng/mL RANKL+complete medium)was added to the osteoclast induction group.1 and 5 μmol/L tabersonine was added for 4 hours,and then osteoclast induction medium was added to the low-and high-dose tabersonine groups,respectively.After 5 days of induction,tartrate-resistant acid phosphatase staining,F-actin staining and RT-PCR were performed.(2)Animal experiments:Twenty C57BL/6J mice were randomly divided into sham operation group,osteolysis group,low-dose tabersonine group and high-dose tabersonine group(n=5 per group).Skull osteolysis model of the skull was established by injecting titanium pellets on the skull surface in the osteolysis group,low-dose tabersonine group and high-dose tabersonine group.On day 2 after model establishment,mice in the low-dose and high-dose tabersonine groups received intraperitoneal injections of 10 and 20 mg/kg tabersonine every 2 days,respectively.2 weeks after surgery,mouse sera were collected for detecting inflammatory factors(interleukin 1β,interleukin 6,and tumor necrosis factor α),and cranial bones were collected for micro-CT scan and bone parameter analysis. RESULTS AND CONCLUSION:(1)Cellular experiments:Tartrate-resistant acid phosphatase staining and F-actin staining showed that compared with the osteoclast induction group,low-dose and high-dose tabersonine significantly inhibited osteoclast activation and bone resorption,and the inhibition was more significant in the high-dose tabersonine group.RT-PCR results showed that compared with the control group,the mRNA expressions of three kinds of inflammatory factors were increased in the osteoclast induction group(P<0.01).Compared with the osteoclast induction group,the mRNA expressions of three kinds of inflammatory factors were decreased in low-and high-dose tabersonine groups(P<0.01),and the decrease was more obvious in the high-dose tabersonine group.(2)Animal experiments:Compared with the sham operation group,the levels of three kinds of inflammatory factors were increased in the osteolysis group(P<0.01).Compared with the osteolysis group,the levels of three kinds of inflammatory factors were decreased in the low-and high-dose tabersonine groups(P<0.05,P<0.01),and the decrease was more obvious in the high-dose tabersonine group.The micro-CT scan results revealed that titanium particles caused the destruction of cranial osteolysis,and tabersonine could inhibit the osteolysis induced by titanium particles,especially in the high-dose tabersonine group.(3)The results confirm that tabersonine can enhance the osteolysis and bone destruction induced by titanium particles by inhibiting the release of inflammatory factors and down-regulating the bone absorption function of osteoclasts.
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BACKGROUND:Toll-like receptors are an important class of pattern recognition receptors that have important functions in pathogen immunity and cytokine synthesis by recognizing specific molecular patterns.Previous studies have found that different types of bone tissue cells also express Toll-like receptors.Activation or inhibition of Toll-like receptors can have significant effects on osteoblast and osteoclast function through multiple pathways. OBJECTIVE:To summarize the expression and action pathways of Toll-like receptors in osteoblasts and osteoclasts,in order to further elucidate the biological mechanisms involved in the regulation of Toll-like receptors under physiological and pathological conditions. METHODS:Relevant literature was retrieved from databases such as PubMed and CNKI as of December 2022.The Chinese and English search terms included"Toll-like receptor,osteoblast,osteoclast,mesenchymal stem cells,macrophage,cytokine,signaling pathway".According to the research needs,the corresponding criteria were established to screen the final literature. RESULTS AND CONCLUSION:(1)Toll-like receptors could directly regulate osteoblast and osteoclast differentiation through the activation of related signaling pathways.(2)Toll-like receptor activation induces cytokine production and exerts regulatory effects.(3)Toll-like receptor activation can affect the survival and migration ability of osteoblasts and osteoclasts.(4)Toll-like receptors in osteoblasts and osteoclasts are activated in certain diseases and pathological settings and are involved in intercellular interactions.
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BACKGROUND:The nuclear factor-κB signaling pathway plays an important role in the pathogenesis of osteoporosis.In recent years,increasing studies have shown that terpenoid herbal monomer compounds can inhibit the activity of bone resorbing cells and promote the differentiation of bone forming cells via the nuclear factor-κB signaling pathway,thus reducing bone resorption and increasing bone formation,which has certain preventive and therapeutic effects on osteoporosis. OBJECTIVE:By analyzing and summarizing the domestic and international literature,to investigate the relationship between nuclear factor-κB signaling pathway and osteoporosis in depth,elucidate the mechanism of terpenoid monomer compounds in regulating the nuclear factor-κB signaling pathway to prevent osteoporosis,and systematically summarize the terpenoid monomer compounds targeting to regulate the nuclear factor-κB signaling pathway to prevent osteoporosis. METHODS:According to the proposed inclusion and exclusion criteria,two researchers searched for relevant articles published from database inception to December 2022 in CNKI and PubMed using the search terms"NF-κB,osteoporosis,osteoblasts,osteoclasts,angiogenesis,traditional Chinese medicine,terpenoid"in Chinese and English,respectively.A third researcher summarized and organized the literature and 75 articles were finally included for a systematic review. RESULTS AND CONCLUSION:The nuclear factor-κB signaling pathway mediates the onset and progression of osteoporosis by regulating the differentiation and proliferation of osteoblasts and osteoclasts,as well as angiogenesis.Activation of the nuclear factor-κB signaling pathway negatively regulates the proliferation and differentiation of osteoblasts.Activation of the nuclear factor-κB signaling pathway enhances osteoclast activity and inhibits osteoblast growth,thereby inhibiting compensatory bone production to maintain bone homeostasis.However,over-activation of the nuclear factor-κB signaling pathway can lead to osteoporosis.The nuclear factor-κB signaling pathway is involved in the"angiogenesis-osteogenesis"coupling by upregulating the expression levels of cytokines such as angiopoietin-1,platelet-derived growth factor BB and vascular endothelial growth factor,which promote the growth of blood vessels in bone.The terpenoid herbal monomer compounds are used in the field of tissue engineering to promote the proliferation and differentiation of bone cells,thereby promoting the growth and repair of bone tissue.Terpenoid herbal monomer compounds can prevent and treat osteoporosis by inhibiting the degradation of nuclear factor-κB inhibitor,blocking nuclear factor-κB/p65 phosphorylation and nuclear translocation,thereby weakening the nuclear factor-κB signaling pathway,promoting osteoblast differentiation and inhibiting osteoclast formation.Currently,research on the regulation of nuclear factor-κB signaling pathway by monomeric compounds of terpenoids to prevent osteoporosis is mainly based on in vitro cellular experiments and animal models,and there is a lack of research on the complex physiological and pathological processes in humans.In the future,more clinical trials and studies are needed to further clarify the mechanism of action and efficacy of the nuclear factor-κB signaling pathway involved in the intervention of osteoporosis.
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BACKGROUND:Reactive oxygen species is a double-edged sword in the development of periodontitis and the regeneration of periodontal tissue.Low concentration of reactive oxygen species induces the differentiation of periodontal fibroblasts,and excessive reactive oxygen species will cause damage to periodontal tissue.In the process of inflammation,the accumulation of reactive oxygen species in periodontal tissue induces damage to cells and tissues through a variety of signaling pathways or through redox reactions. OBJECTIVE:To review the double-edged sword effect of reactive oxygen species in periodontitis and periodontal tissue regeneration,thereby providing potential targets and treatment ideas for the clinical treatment of periodontitis and periodontal tissue regeneration. METHODS:Databases of CNKI and PubMed were searched for relevant articles published from April 1990 to April 2023 with the key words of"periodontal tissue engineering,periodontal defect,regeneration of periodontal tissue,chronic periodontitis,reactive oxygen species,oxidative stress,antioxidative stress,oxidative injuries,free radicals,reactive nitrogen species"in Chinese and English,respectively.By reading the titles and abstracts,repetitive studies or irrelevant literatures were excluded.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Reactive oxygen species are a kind of free radicals with high reactivity.When bacteria invade,reactive oxygen species are released in large quantities by the respiratory explosion of neutrophils and play a double-edged sword role in the body through their redox reactions or as pleiotropic physiological signal transmitters.In periodontitis,low concentrations of reactive oxygen species can kill invading pathogenic bacteria,but high concentrations of reactive oxygen species promote the secretion of inflammatory factors through JNK,RANK,Wnt/β-Catenin and other pathways,promote immune damage or directly damage tissues through oxidative reactions or through other ways to aggravate periodontitis.In the process of periodontal tissue regeneration,low concentrations of reactive oxygen species can promote the proliferation and differentiation of periodontal ligament stem cells through Nrf2 and other pathways and can promote the secretion of vascular endothelial growth factor to promote vascular regeneration.This provides seeds and a nutrient environment for periodontal tissue regeneration,which is extremely important for promoting periodontal tissue regeneration.However,high concentrations of reactive oxygen species will reduce the activity of periodontal ligament stem cells and damage endothelial cells,which are not conducive to vascular regeneration.This will inhibit wound healing and periodontal tissue regeneration.Therefore,it is important to explore the role of reactive oxygen species in the development of periodontitis and periodontal tissue regeneration and to discover the potential mechanism of its action and to explore the appropriate concentration for its role in reducing periodontal inflammation and promoting periodontal tissue regeneration for the future treatment of periodontitis and periodontal tissue regeneration in clinical practice.Using reactive oxygen species as a target to explore ways to reduce periodontal inflammation and promote periodontal ligament stem cell activity and vascular regeneration may become a clinically effective method for treating periodontitis and promoting periodontal tissue regeneration.
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BACKGROUND:In recent years,numerous studies have shown that long non-coding RNAs(lncRNAs)have an important role in the pathogenesis of periodontitis,including the immune response process and the biological activity and function of cells(periodontal stem cells and osteoblasts).Researchers attempt to regulate periodontal inflammation and periodontal regeneration by regulating lncRNA expression levels. OBJECTIVE:To review the progress of research on lncRNAs in periodontitis,thereby advancing the research of lncRNAs in periodontitis. METHODS:The first author searched PubMed,China National Knowledge Infrastructure(CNKI),Web of Science database,and WanFang Database for relevant literature published up to March 2023."Long non-coding RNA,lncRNA,periodontitis,periodontium,immunity,inflammation,periodontal ligament stem cells,osteoclasts,osteogenic differentiation,bone resorption,bone formation,recurrence,hypoxia,oxidative stress,static mechanical strain"were used as the Chinese search terms."lncRNA,periodontitis,periodontal,immunity,inflammation,periodontal membrane stem cells,osteoclasts,osteogenic differentiation,bone resorption,bone formation,recurrence,hypoxia,oxidative stress,static mechanical strain"were used as the English search terms.The title and abstract of each paper were read for initial screening,and 87 papers were finally selected for inductive analysis. RESULTS AND CONCLUSION:Periodontal pathogens stimulate the body,leading to immune imbalance that triggers inflammatory response and destroy periodontal tissue,and lncRNAs are involved in its regulatory mechanism.LncRNAs are involved in the pro-inflammatory regulation of periodontal ligament cells in an inflammatory environment,and their effects on osteoclast differentiation are regulated through ceRNA mechanism,which provides new clues for exploring the pathogenesis of periodontitis.For B cells and macrophages,lncRNAs can regulate the infiltration,cell activity and function of their subsets in periodontitis.LncRNAs participate in the immune response related to periodontitis mainly through two pattern recognition receptors,Toll-like receptors and NOD-like receptors,and nuclear factor-κB signaling pathway.To investigate whether lncRNAs can be used as a biomarker of periodontitis has great value in the diagnosis and prognosis of periodontitis.Animal experiments have demonstrated that the role of lncRNAs in periodontitis can be reversed by modulating the expression level of lncRNAs and thus lncRNAs act as an anti-inflammatory agent,which is of great value for the study of immunotherapy in periodontitis.The regulation of lncRNAs on periodontal ligament stem cells is mainly realized through endogenous competition mechanism and various signaling pathways,and its effects are influenced by various factors,such as inflammatory environment,mechanical strain,hypoxia and oxidative stress.Research on related mechanisms through these related factors provides new ideas for the treatment of periodontitis.
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BACKGROUND:With the aging of the global population,the incidence rate of osteoporosis is also increasing.It is very important to further understand its pathogenesis and propose new therapeutic targets.Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases,such as inflammatory arthritis,osteoporosis and osteoarthritis. OBJECTIVE:To summarize the previous studies on the mechanism of ferroptosis in osteoporosis,so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS:The first author used the computer to search the documents published from 2000 to 2022 in CNKI,WanFang,VIP,PubMed and Web of Science with the key words of"ferroptosis,osteoporosis,osteoblasts,osteoclasts,iron chelators,reactive oxygen species,nuclear factor erythroid 2-related factor 2,heme oxygenase-1,glutathione peroxidase 4,review"in Chinese and English.A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:Ferroptosis is significantly different from necrosis,apoptosis and autophagy.In terms of cell morphology and function,it does not have the morphological characteristics of typical necrosis,nor does it have the characteristics of traditional apoptosis,such as cell contraction,chromatin condensation,the formation of apoptotic bodies and the disintegration of cytoskeleton.Contrary to autophagy,ferroptosis does not form a classical closed bilayer membrane structure(autophagic vacuole).Morphologically,ferroptosis is mainly manifested by obvious contraction of mitochondria,increased membrane density,and reduction or disappearance of mitochondrial cristae,which are different from other cell death modes.Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation,leading to osteoporosis.Iron overload interferes with the differentiation of stem cells to osteoblasts,leading to a weakened osteoblast function and further imbalance of bone metabolism in the body,which eventually leads to osteoporosis.Stimulated by iron overload,osteoclast bone resorption is enhanced and bone loss exceeds new bone formation.Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts.Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation.Antioxidants can prevent reactive oxygen species production and inhibit bone absorption,thus improving bone metabolism and effectively preventing osteoporosis.
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BACKGROUND:Shikonin contributes to the promotion of bone defect repair and the treatment of osteoporosis. OBJECTIVE:To summarize the application potential of shikonin and its derivatives in oral soft and hard tissue regeneration. METHODS:A literature review was conducted in databases such as PubMed,Web of Science,Wanfang,China National Knowledge Infrastructure(CNKI),and VIP,spanning articles from 2002 to 2023.The search terms were"shikonin,oral cavity,periodontitis,antibacterial,bone formation,osteoclast,osteoporosis,toxicology"in Chinese and English. RESULTS AND CONCLUSION:Shikonin and its derivatives possess anti-inflammatory effects,inhibit periodontal pathogens such as Porphyromonas gingivalis,promote periodontal wound healing,and regenerate alveolar bone tissue.Shikonin formulations can be used to treat oral diseases such as aphthous ulcers and oral candidiasis.These findings suggest a promising future for shikonin and its derivatives in treating periodontal diseases,preventing oral ailments,and promoting the regeneration of both soft and hard periodontal tissues.Further research is needed to explore how to combine shikonin with tissue engineering to achieve quicker healing of oral soft and hard tissues.
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BACKGROUND:Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis.During the pathogenesis of osteoporosis,miR-155 knockdown activates adenosine phosphate-dependent protein kinase(AMPK)by increasing the expression of leptin receptors,thereby inhibiting osteoclast differentiation and bone resorption.However,the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE:To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS:RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative(PPD)(1.0,2.5,5.0,10.0 IU/mL)and transfected with negative control(NC)sequence or miR-155 inhibitor,NC siRNA sequence or LEPR siRNA sequence.Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts.Fluorescence quantitative PCR was used to detect the expression of miR-155.Western blot was used to detect the expression of LEPR and p-AMPK.Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION:Compared with the control group,the number of osteoclasts and the expression level of miR-155 significantly increased,while the expression level of LEPR and p-AMPK significantly decreased in 2.5,5.0,and 10.0 IU/mL PPD groups(P＜0.05).Compared with NC+5.0 IU/mL PPD group,the number of osteoclasts and the expression level of miR-155 significantly decreased,while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).Compared with the NC group,the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group,and decreased in the miR-155 mimic group(P＜0.05).Compared with si-NC+miR-155 inhibitor+5.0 IU/mL PPD group,the expression level of miR-155 had no significant change,the number of osteoclasts significantly increased,and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).To conclude,tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation.
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BACKGROUND:Tumor necrosis factor-α is a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body.The current study concluded that tumor necrosis factor-α has significant biological effects on a variety of bone tissue cells. OBJECTIVE:To summarize the expression and action pathways of tumor necrosis factor-α in osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-α on bone tissue cells. METHODS:PubMed and CNKI were searched until March 2023,and the Chinese search terms included"tumor necrosis factor α,osteoblast,osteoclast,osteoclast,osteoprogenitor";the English search terms included"TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell".The corresponding criteria were established according to the research needs,and the final literature was screened.Finally,77 articles were included for review. RESULTS AND CONCLUSION:(1)Tumor necrosis factor-α is participating in regulating the recruitment,appreciation,and differentiation of osteoprogenitor cells,but leads to osteoprogenitor cell stripping and death under specific environments.It also participates in bone resorption directly or indirectly through secreted enzymes.(2)Tumor necrosis factor-α can increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments.(3)Tumor necrosis factor-α can inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway,inhibiting the expression of transcription factors such as RUNX2 and Osterix,and inducing apoptosis and necrotizing apoptosis in osteoblasts.(4)Tumor necrosis factor-α inhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL,SOST,and DKK1,while enhancing apoptosis of the osteocytes,as well as bone resorption around the apoptotic bone tissue.(5)Taken together,the effect of tumor necrosis factor-α in bone tissue is mainly to inhibit osteogenesis and promote osteoclastosis.The biological effect of tumor necrosis factor-α in bone tissue cells is usually dependent on the activation of tumor necrosis factor receptor and nuclear factor-κB signaling pathways.(6)The interaction of tumor necrosis factor-α with other tissue cell types surrounding bone tissue and its role in bone immune regulation still deserve attention in future studies.
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BACKGROUND:Some studies have found that local application of alendronate can promote osteogenesis,but less is reported on the process of distraction osteogenesis. OBJECTIVE:To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS:Thirty-six male New Zealand white rabbits were randomly divided into groups A,B and C(n=12 per group)after operation and rapid distraction(3-day delay period followed by 3-day distraction at 1.5 mm/12 hours).At the 1st,3rd and 7th days of the consolidation period,animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B,while those in group C were treated as controls.CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period.After the radionuclide scanning was completed at the 4th week,several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining.A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION:CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C.At the 4th week,the bone mineral density in group B was(0.092±0.010)g/cm2,which was 1.26 times higher than that in group A(P＜0.001)and 1.28 times higher than that in group C(P＜0.001).At the 8th week,the bone mineral density in group B was(0.175±0.029)g/cm2,which was 1.38 times higher than that in group A(P＜0.001)and 1.45 times higher than that in group C(P＜0.001).Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A(P＜0.001)and 2.21 times more than that in group B(P＜0.001).The radionuclide intensity was higher in group C than in groups A and B.Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C.The maximum biomechanical load in group B was(158.48±23.21)N,which was 1.26 times higher than that in group A(P=0.007)and 1.31 times higher than that in group C(P=0.003).To conclude,the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals.
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BACKGROUND:The development of steroid-induced osteonecrosis of the femoral head is a complex process involving multiple mechanisms.There is still no standard therapeutic drug for early intervention of this disease.Current studies have shown that baicalein has various pharmacological activities such as regulating lipid metabolism,bone metabolism,apoptosis and anti-oxidative stress,which provides an idea for the prevention and treatment of steroid-induced osteonecrosis of the femoral head. OBJECTIVE:To observe the preventive effect of baicalein against steroid-induced osteonecrosis of the femoral head and to investigate its possible mechanism. METHODS:Thirty-six 10-week-old male Sprague-Dawley rats were randomly divided into three groups(n=12 per group):blank control group,model group,and baicalein intervention group.In the model group and baicalein intervention group,intraperitoneal lipopolysaccharide and intramuscular injection of methylprednisolone sodium succinate were performed for modeling,while normal saline was used as a substitute for the modeling drug in the blank control group.Baicalein 300 mg/kg was administered by gavage(once a day for 6 weeks)at the time of initial intramuscular glucocorticoid injection in the baicalein intervention group,and baicalein was replaced by normal saline in the other two groups.The serum level of malondialdehyde in rats was detected at 2 weeks of the experiment.Blood lipid indicators and bone formation metabolic markers were detected at 6 weeks of the experiment,the histomorphometric changes of the femoral head were analyzed by hematoxylin-eosin staining,anti-tartaric acid phosphatase staining and TUNEL staining,and the femoral head was subjected to Micro-CT scanning and three-dimensional reconstruction of the bone in order to analyze the alterations of bone tissue structure and parameters. RESULTS AND CONCLUSION:The serum levels of malondialdehyde,triglyceride,β-collagen type Ⅰ carboxy-terminal peptide were increased and the serum levels of bone specific alkaline phosphatase and pre-collagen type Ⅰ amino-terminal peptide were decreased in the model group compared with the blank control group(P＜0.05).The serum level of malondialdehyde decreased in the baicalein intervention group compared with the model group(P＜0.05),but there was no significant difference between the baicalein intervention group and blank control group(P＞0.05).The serum level of triglyceride was higher in the baicalein intervention group than the blank control group(P＜0.05),but had no significant difference between the baicalein intervention group and model group(P＞0.05).There were also no significant differences in the levels of bone specific alkaline phosphatase and β-collagen type Ⅰ carboxy-terminal peptide between the baicalein intervention group and the other two groups(P＞0.05).The serum level of the baicalein intervention group was lower in the baicalein intervention group than the blank control group(P＜0.05)but had no significant difference between the baicalein intervention group and model group(P＞0.05).Histomorphological analysis of the femoral head showed that the rate of bone empty lacuna,osteoclast counting and cell apoptosis rate in the femoral head of model group rats were significantly higher than those of the other two groups(P＜0.05).There was a significant increase in the number of adipocytes in the bone marrow cavity of the femoral head,bone trabeculae were thinned and sparsely arranged with more disruptions in the continuity.The incidence of osteonecrosis was higher in the model group(75%)than in the baicalein intervention group(25%;bilateral and unilateral exact significance results were both 0.05).There was also an increase in the number of adipocytes in the bone marrow cavity of the femoral head in the baicalein intervention group,and the trabecular changes were roughly similar to those in the model group.Micro-CT results showed that bone volume fraction,trabecular thickness,trabecular number,and bone mineral density decreased and trabecular separation increased in the model group compared with the blank control group(P＜0.05).Overall significant bone mass loss was observed in the model group.Bone tissue parameters in the baicalein intervention group were significantly improved than those in the model group,which were reflected in bone volume fraction,trabecular thickness and trabecular separation(P＜0.05),and trabecular number and bone mineral density had no significant difference between the baicalein intervention group and blank control group(P＞0.05).Although baicalein failed to significantly ameliorate dyslipidemia and promote bone formation in rats with steroid-induced osteonecrosis of the femoral head,it could reduce the incidence of steroid-induced osteonecrosis of the femoral head by reducing oxidative stress damage,decreasing cell apoptosis,inhibiting osteoclasts,suggesting its effectiveness in the early prevention of steroid-induced osteonecrosis of the femoral head.
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BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.
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BACKGROUND:Interleukin-8 is an important cytokine that has been found to play an important role in bone regeneration through multiple pathways. OBJECTIVE:To comprehensively review the action mechanism of interleukin-8 effects on bone regeneration to provide ideas for the following studies on interleukin-8. METHODS:By searching the China National Knowledge Infrastructure database for articles published from January 1999 to February 2023 and PubMed database for articles published from January 1985 to February 2023 reporting the role of interleukin-8 in bone-associated cells and vascularisation.Chinese and English search terms were"interleukin-8,bone repair,bone metabolism,mesenchymal stem cells,osteoblasts,osteoclasts,vascularization".The initial review yielded 508 articles in English and Chinese,and a total of 51 articles were included for review and analysis according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:According to the existing research,interleukin-8 can promote bone cell regeneration and assist bone healing through multiple pathways,which is mainly divided into three aspects:(1)Promote the proliferation and differentiation of bone cells such as mesenchymal stem cells and osteoblasts,and promote the development of cells in the direction of promoting bone healing;(2)interleukin-8 can promote angiogenesis and provide sufficient nutrition and oxygen for bone tissue,thus further improving the quality and stability of bone healing.(3)The appearance of interleukin-8 facilitates the expression of hypoxia-inducible factor-1α,vascular endothelial growth factor,and matrix metalloproteinase,which can create a microenvironment conducive to bone regeneration,thus promoting the regeneration and repair of bone tissue.In summary,interleukin-8 plays an important role in bone healing by promoting osteoblast proliferation and differentiation,facilitating angiogenesis and improving the mechanical properties of bone regeneration,as well as influencing bone metabolism through osteoclasts,mesenchymal stem cells,and other action sites.
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BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.
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BACKGROUND:Previous studies have demonstrated that icariin has important roles in promoting bone formation and inhibiting bone resorption,but its effects on osteoporosis-mediated bone pain have not been reported. OBJECTIVE:To investigate the possible mechanism of icariin alleviating bone pain in postmenopausal senile osteoporosis. METHODS:(1)Animal experiment:200 C57BL/6 mice were randomly divided into 4 groups:sham group(n=50),model group(n=50),icariin treatment group(n=50),and carbonic anhydrase Ⅱ inhibitor(Brinzolamide)treatment group(n=50).Ovariectomy was performed on C57BL/6 mice to establish a postmenopausal osteoporosis model in all groups except the sham group.The icariin group was given icariin on the second day after modeling,and pain behavior tests(Von Frey,Hot Plate,and Tail Flick tests)were performed every 2 weeks for 20 weeks.After sampling,bone mass was detected by microCT,osteoclast activity was detected by hematoxylin-eosin and tartrate-resistant acid phosphatase staining,and neuronal morphology and related ion channel expression were detected by tissue immunofluorescence staining.(2)Cell experiment:Osteoclast precursor cells derived from mouse bone marrow were extracted and induced to differentiate into osteoclasts using the RANKL/M-CSF system in vitro and supplemented with icariin of different concentrations(1 and 10 μmol/L).Tartrate-resistant acid phosphatase staining was used to detect osteoclast differentiation,ghost pen cyclic peptide staining was used to detect osteoclast actin ring,bone plate absorption assay was used to detect osteoclast osteophagy function,pH value of the system was detected by pH meter,and expression of osteoclast differentiation-related proteins was detected by western blot.In addition,mouse dorsal root ganglion-derived nerve cells were extracted and treated with icariin.Cell counting kit-8 was used to detect neuronal activity and CGRP staining was used to detect neuronal morphology. RESULTS AND CONCLUSION:Compared with the model group,the icariin treatment group had higher bone mineral density,fewer tartrate-resistant acid phosphatase-positive osteoclasts in bone tissue,decreased neuronal activity,and decreased neuronal transient receptor potential vanilloid subtype 1 channel and carbonic anhydrase Ⅱ expression.Behavioral results showed that the icariin treatment group was less sensitive to pain than the model group.Icariin inhibited osteoclast differentiation and bone phagocytosis in vitro.Icariin enhanced the activity of dorsal root ganglion neurons and inhibited the expression of calcitonin gene-related peptide and transient receptor potential vanilloid subtype 1 channels in dorsal root ganglia in a relatively non-toxic pH range.To conclude,icariin alleviates bone pain caused by postmenopausal osteoporosis by regulating the acidic microenvironment through its effect on osteoclasts.