Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex b...Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex bone defects.However,final bone repair outcomes may be adversely affected by poor osteogenic capacity and risk of infection.Consequently,therapeutic methods are required that reduce bacterial contamination and increase the use of osteogenic biomaterials.Herein,we report the preparation of poly(lactic acid-coglycolic acid)(PLGA)microspheres coloaded with magnesium(Mg^(2+))and gallium(Ga^(3+))ions(Mg-Ga@PLGA),which can fill irregular bone defects and show good biosafety.During in vitro testing,Mg-Ga@PLGA not only showed a synergistic effect on promoting osteogenic differentiation but also inhibited osteoclastic differentiation.Moreover,we found that Mg-Ga@PLGA demonstrated an antibacterial effect.During in vivo testing,Mg Ga@PLGA exhibited strong in situ osteogenic ability.In conclusion,Mg-Ga@PLGA has good potential for treating bone defects at risk of infection.展开更多
BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is characterized by lipid accumulation in hepatocytes and is closely associated with oxidative stress.Increasing clinical evidence indicates that MAFLD is link...BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is characterized by lipid accumulation in hepatocytes and is closely associated with oxidative stress.Increasing clinical evidence indicates that MAFLD is linked to bone metabolic disorders,including osteoporosis.Recent studies indicate that the expression profiles of liver circular RNAs(circRNAs)are altered in MAFLD.However,the effects of these changes on bone metabolism remain poorly understood.AIM To investigate the effects and mechanism of differently expressed circRNAs secreted by the liver on osteogenic differentiation in MAFLD.METHODS RNA sequencing was performed to identify highly expressed circRNAs in the liver,validated by quantitative real-time reverse transcription polymerase chain reaction,and localized using fluorescence in situ hybridization(FISH).A mouse model induced by a high-fat diet was used to simulate MAFLD.RESULTS CircSOD2 was significantly upregulated in liver tissues and primary hepatocytes from subjects with MAFLD.CircSOD2 was induced by oxidative stress and attenuated by antioxidants in the mouse model.In addition,circSOD2 was delivered from hepatocytes to bone marrow mesenchymal stem cells(BMSCs).Furthermore,circSOD2 inhibited the osteogenic differentiation of BMSCs and in vivo bone formation by sponging miR-29b.Moreover,miR-29b inhibition reversed the stimulatory effect of circSOD2 silencing on osteogenic differentiation of BMSCs and in vivo bone formation.Mechanistically,the interaction between circSOD2 and miR-29b confirmed through a luciferase reporter assay and the co-localization in the cytoplasm evidenced by FISH indicated that circSOD2 acted as a sponge for miR-29b.CONCLUSION This study provides a novel mechanism underlying the liver-bone crosstalk,demonstrating that circSOD2 upregulation in hepatocytes,induced by oxidative stress,inhibits osteogenic differentiation of BMSCs by sponging miR-29b.These findings offer a better understanding of the relationship between MAFLD and osteoporosis.展开更多
Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temp...Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.展开更多
Magnesium(Mg)alloys with biodegradability and excellent mechanical properties are in high demand for applications in guided bone regeneration(GBR).However,the clinical application of Mg alloys is hindered by infection...Magnesium(Mg)alloys with biodegradability and excellent mechanical properties are in high demand for applications in guided bone regeneration(GBR).However,the clinical application of Mg alloys is hindered by infection risks and limited osteogenesis.Herein,a structure-functional integrated Mg-Ca/Mg-Cu bilayer membrane was rolled at 150℃through various single-pass reductions by using online heating rolling.The Mg-Cu layer was specifically engineered to exhibit antibacterial properties tailored for gingival tissue,while the Mg-Ca layer was designed to support bone regeneration within the defect cavity.The bilayer membrane demonstrated a flexural yield strength of 421.0 MPa and a modulus of 58.6 GPa,indicating exceptional deformation resistance.Furthermore,it maintained notable structural stability by retaining 86.4%of its volume after 21 days in Hanks'solution.In vitro results revealed that the bilayer membrane exhibited favorable biocompatibility and promoted osteogenesis via the synergetic effect of released Mg^(2+)and Ca^(2+)ions.The rapid release of Cu^(2+)ions and the creation of an alkaline environment further improved antibacterial properties,potentially preventing postoperative infections.Additionally,in an in vivo rat calvarial defect model,the membrane demonstrated its capability to stimulate new bone formation.In summary,the Mg-Ca/Mg-Cu bilayer membrane exhibited outstanding mechanical stability,favorable corrosion rates,extraordinary osteogenic and antibacterial activity simultaneously.Consequently,it holds promise as a robust barrier membrane in GBR applications.展开更多
Guided bone regeneration(GBR)membranes are extensively utilized in dental implantation.However,the existing GBR membranes showed insufficient space-maintaining capability and poor bone promoting ability,affecting the ...Guided bone regeneration(GBR)membranes are extensively utilized in dental implantation.However,the existing GBR membranes showed insufficient space-maintaining capability and poor bone promoting ability,affecting the effectiveness of clinical bone augmentation,which in turn resulted in poor implant outcomes and even failure.In this study,we designed a novel magnesium reinforced sandwich structured composite membrane,consisting of an inner magnesium scaffold and a PLGA/collagen hybrid(mixture of poly(lactic-co-glycolic acid)and collagen)top and bottom layer.The magnesium scaffold provided mechanical support and released Mg^(2+)to enhance osteogenesis.The PLGA/collagen hybrid regulated membrane degradation and improved biocompatibility,promoting cell adhesion and proliferation(P<0.05).The PLGA/collagen hybrid regulated the release of magnesium ions,such that the MgP10C(mass ratios of PLGA and collagen=100:10)group showed the best in vitro osteogenic effect.Further mechanism exploration confirmed that MgP10C membranes significantly enhanced bone defect repair via the MAPK/ERK 1/2 pathway by the Mg^(2+)released from the composite membranes.In rat calvarial defect and rabbit alveolar defect model(P<0.05),the in vivo osteogenic effect of the MgP10C group was superior to that of other groups.Finite element analysis models validated the support effect of composite membranes,demonstrating lower stress and a significant reduction in strain on the bone graft in the MgP10C group.In conclusion,the magnesium-reinforced sandwich structure composite membrane,with its spacemaintaining properties and osteoinductive activity,represents a new strategy for GBR and enhancing osteogenic potential that meets directly clinical needs.展开更多
Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration w...Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration when designing biomedical implants. In this research, ordered structures with Schottky heterojunction functional unit (OSSH) were constructed on titanium implant surfaces for bone regeneration regulation. The Schottky heterojunction functional unit is composed of periodically distributed titanium microdomain and titanium oxide microdomain with different carrier densities and surface potentials. The OSSH regulates the M2-type polarization of macrophages to a regenerative immune response by activating the PI3K-AKT-mTOR signal pathway and further promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells. This work provides fundamental insights into the biological effects driven by the Schottky heterojunction functional units that can electrically modulate osteogenesis.展开更多
Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,th...Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,the additional functions of the bone vasculature,such as the secretion of various factors and the regulation of bone-related signaling pathways,are essential for maintaining bone health.In the bone microenvironment,bone tissue cells play a critical role in regulating angiogenesis,including osteoblasts,bone marrow mesenchymal stem cells(BMSCs),and osteoclasts.Osteogenesis and bone angiogenesis are closely linked.The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis.Long noncoding RNAs(lncRNAs)are involved in various physiological processes,including osteogenesis and angiogenesis.Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis.However,the mechanism by which lncRNAs regulate angiogenesis-osteogenesis crosstalk remains unclear.In this review,we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health,aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.展开更多
Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role ...Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role of matrix-embedded osteocytes in OI pathogenesis remains largely unknown.Homozygous human SP7(c.946 C>T,R316C)mutation results in a recessive form of OI characterized by fragility fractures,low bone mineral density and osteocyte dendrite defects.To better understand how the OI-causing R316C mutation affects the function of SP7,we generated Sp7^(R342C)knock-in mice.Consistent with patient phenotypes,Sp7^(R342C/R342C)mice demonstrate increased cortical porosity and reduced cortical bone mineral density.Sp7^(R342C/R342C)mice show osteocyte dendrite defects,increased osteocyte apoptosis,and intracortical bone remodeling with ectopic intracortical osteoclasts and elevated osteocyte Tnfsf11 expression.展开更多
BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of ...BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.展开更多
Magnesium(Mg)and its alloys have similar densities and elastic moduli to natural bone,making them an excellent choice for orthopedic implants.However,Mg alloys are prone to electrochemical corrosion,which often leads ...Magnesium(Mg)and its alloys have similar densities and elastic moduli to natural bone,making them an excellent choice for orthopedic implants.However,Mg alloys are prone to electrochemical corrosion,which often leads to implant failure and hinders the further development of Mg alloys due to bacterial infection around the implant.This work aims to enhance the corrosion resistance of Mg alloys,and provide theoretical guidance for solving the problem that Mg-based orthopedic implants are susceptible to bacterial infection and,thus,implant failure.In order to solve the corrosion problem,the Mg alloy AZ91D was used as the substrate,and a compact and uniform MgAlCu-layered double hydroxide(Mg(Cu)-LDH)was prepared on its surface using a hydrothermal method.The Mg(Cu)-LDH provides a barrier between the AZ91D and corrosive liquid,which effectively protects the Mg substrate from being corroded.The Mg(Cu)-LDH shows great cell viability for MC3T3-E1 cells.The Cu^(2+)and Mg^(2+) in the coating also endow the Mg(Cu)-LDH/AZ91D with antibacterial properties,showing strong antibacterial effects on both E.coli and S.aureus with antibacterial rates over 85%.Finally,in vivo results indicated that a LDH-coated implant had no systemic effects on the hearts,livers,spleens,lungs or kidneys.It was shown that 4 weeks after surgery the ratio of bone volume to tissue volume(BV/TV)of the LDH implant was 24%,which was 1.7 times that observed for AZ91D.展开更多
Biodegradable magnesium-matrix composites(BMMCs)added with bone-like compounds such as hydroxyapatite(HA)have promising orthopedic application potential,but the in vivo results of BMMCs are insufficient,and the differ...Biodegradable magnesium-matrix composites(BMMCs)added with bone-like compounds such as hydroxyapatite(HA)have promising orthopedic application potential,but the in vivo results of BMMCs are insufficient,and the difference between in vitro and in vivo are not clarified.In this work,Mg-Zn-Nd-Zr/(10/15/20wt%)HA(Ca_(10)(PO_(4))_(6)OH_(2))composites were prepared through friction stirring processing(FSP).It was found that corrosion rate of the composites increased with increase of the HA content,where the corrosion rate from hydrogen evolution of the Mg/10wt%HA was about 0.107 mm/y,showing better corrosion resistance compared with other BMMCs,and the agglomeration of HA powders significantly aggravated the localized corrosion.The ALP specific activity of the MC3T3-E1 cells cultured for14 days with Mg/10wt%HA(2.12 IU/mg)was higher than that of the matrix(1.85 IU/mg),but there was no difference with the FSP group(2.13 IU/mg).In the early implantation of the rabbit femur,bone volume fraction(BV/TV)of Mg/10wt%HA was 10.69,which was higher than that of the FSP group(6.35).The histological staining showed that the Mg/10wt%HA implant was surrounded by more trabecular bone tissue,exhibiting better osteoinductive regeneration.The Mg-Zn-Nd-Zr/HA composites exhibit higher osteogenic activity in vivo differently from in vitro osteogenic expression.展开更多
Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed ...Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed through genetic studies. We present a case of osteogenesis imperfecta suspected during obstetrical ultrasound at 19 weeks’ gestation, which was later confirmed radiographically through computed tomography. Due to the severity of the condition, therapeutic termination of pregnancy was indicated.展开更多
Aim Understanding the response of mesenchymal stem cells （MSCs） to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis. Method...Aim Understanding the response of mesenchymal stem cells （MSCs） to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis. Methodology In this study, a single period of cyclic mechanical stretch （0.5 Hz, 2,000 με） was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase （ALP） activity was examined. The mRNA expression of six bone-related genes （Ets-1, bFGF, IGF-Ⅱ, TGF-β, Cbfal and ALP） was detected using real-time quantitative RT-PCR. Results The results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfal expression became elevated later. The temporal expression pattem of ALP coincided perfectly with Cbfal. Conclusion The results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts, and that these bone-related genes may play different roles in the response of MSCs to mechanical stimulation.展开更多
Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation....Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.展开更多
Objective： We investigated the effects of intermittent negative pressure on osteogenesis in human bone marrowderived stroma cells （BMSCs） in vitro. Methods： BMSCs were isolated from adult marrow donated by a hip o...Objective： We investigated the effects of intermittent negative pressure on osteogenesis in human bone marrowderived stroma cells （BMSCs） in vitro. Methods： BMSCs were isolated from adult marrow donated by a hip osteoarthritis patient with prosthetic replacement and cultured in vitro. The third passage cells were divided into negative pressure treatment group and control group. The treatment group was induced by negative pressure intermittently （pressure： 50 kPa, 30 min/times, and twice daily）. The control was cultured in conventional condition. The osteogenesis of BMSCs was examined by phase-contrast mi- croscopy, the determination of alkaline phosphatase （ALP） activities, and the immunohistochemistry of collagen type 1. The mRNA expressions of osteoprotegerin （OPG） and osteoprotegerin ligand （OPGL） in BMSCs were analyzed by real-time polymerase chain reaction （PCR）. Results： BMSCs showed a typical appearance of osteoblast after 2 weeks of induction by intermittent negative pressure, the activity of ALP increased significantly, and the expression of collagen type I was positive. In the treatment group, the mRNA expression of OPG increased significantly （P〈0.05） and the mRNA expression of OPGL decreased significantly （P〈0.05） after 2 weeks, compared with the control. Conclusion： Intermittent negative pressure could promote osteogenesis in human BMSCs in vitro.展开更多
YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone h...YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.展开更多
Ginsenoside Rb1, the effective constituent of ginseng, has been demonstrated to play favorable roles in improving the immunity system. However, there is little study on the osteogenesis and angiogenesis effect of Gins...Ginsenoside Rb1, the effective constituent of ginseng, has been demonstrated to play favorable roles in improving the immunity system. However, there is little study on the osteogenesis and angiogenesis effect of Ginsenoside Rb1. Moreover, how to establish a delivery system of Ginsenoside Rb1 and its repairment ability in bone defect remains elusive. In this study, the role of Ginsenoside Rb1 in cell viability, proliferation, apoptosis, osteogenic genes expression, ALP activity of rat BMSCs were evaluated firstly. Then,micro-nano HAp granules combined with silk were prepared to establish a delivery system of Ginsenoside Rb1, and the osteogenic and angiogenic effect of Ginsenoside Rb1 loaded on micro-nano HAp/silk in rat calvarial defect models were assessed by sequential fluorescence labeling, and histology analysis, respectively. It revealed that Ginsenoside Rb1 could maintain cell viability, significantly increased ALP activity, osteogenic and angiogenic genes expression. Meanwhile, micro-nano HAp granules combined with silk were fabricated smoothly and were a delivery carrier for Ginsenoside Rb1. Significantly, Ginsenoside Rb1 loaded on micro-nano HAp/silk could facilitate osteogenesis and angiogenesis. All the outcomes hint that Ginsenoside Rb1 could reinforce the osteogenesis differentiation and angiogenesis factor’s expression of BMSCs. Moreover, micro-nano HAp combined with silk could act as a carrier for Ginsenoside Rb1 to repair bone defect.展开更多
In order to identify the differentially expressing gene of bone marrow mesenchymal stem cells （MSCs） stimulated by electromagnetic field （EMF） with osteogenesis microarray analysis, the bone marrow MSCs of SD rats...In order to identify the differentially expressing gene of bone marrow mesenchymal stem cells （MSCs） stimulated by electromagnetic field （EMF） with osteogenesis microarray analysis, the bone marrow MSCs of SD rats were isolated and cultured in vitro. The third-passage cells were stimulated by EMFs and total RNA was extracted, purified and then used for the synthesis of cDNA and cRNA. The cRNA of stimulated group and the control group was hybridized with the rat oligo osteogenesis microarray respectively. The hybridization signals were acquired by using X-ray film after chemiluminescent detection and the data obtained were analyzed by employing the web-based completely integrated GEArray Expression Analysis Suite. RT-PCR was used to identify the target genes： Bmp1, Bmp7, Egf and Egfr. The results showed that 19 differentially expressing genes were found between the stimulated group and the control group. There were 6 up-regulated genes and 13 down-regulated genes in the stimulated group. Semi-quantitative RT-PCR confirmed that the expressions of Bmpl, Bmp7 mRNA of the stimulated group were up-regulated （P〈0.05） and those of Egf, Egfr were down-regulated （P〈0.05）. It was suggested that the gene expression profiles of osteogenesis of the bone marrow MSCs were changed after EMF treatment. It is concluded that the genes are involved in skeletal development, bone mineral metabolism, cell growth and differentiation, cell adhesion etc.展开更多
Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the r...Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.展开更多
Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medi...Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P <0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.31971106,BWS21L013,and 21WS09002).
文摘Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex bone defects.However,final bone repair outcomes may be adversely affected by poor osteogenic capacity and risk of infection.Consequently,therapeutic methods are required that reduce bacterial contamination and increase the use of osteogenic biomaterials.Herein,we report the preparation of poly(lactic acid-coglycolic acid)(PLGA)microspheres coloaded with magnesium(Mg^(2+))and gallium(Ga^(3+))ions(Mg-Ga@PLGA),which can fill irregular bone defects and show good biosafety.During in vitro testing,Mg-Ga@PLGA not only showed a synergistic effect on promoting osteogenic differentiation but also inhibited osteoclastic differentiation.Moreover,we found that Mg-Ga@PLGA demonstrated an antibacterial effect.During in vivo testing,Mg Ga@PLGA exhibited strong in situ osteogenic ability.In conclusion,Mg-Ga@PLGA has good potential for treating bone defects at risk of infection.
基金Supported by the National and Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Project,No.GZYZJ-KJ-24080the Medical Science and Technology Project of Zhejiang Province,No.2024XY228.
文摘BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is characterized by lipid accumulation in hepatocytes and is closely associated with oxidative stress.Increasing clinical evidence indicates that MAFLD is linked to bone metabolic disorders,including osteoporosis.Recent studies indicate that the expression profiles of liver circular RNAs(circRNAs)are altered in MAFLD.However,the effects of these changes on bone metabolism remain poorly understood.AIM To investigate the effects and mechanism of differently expressed circRNAs secreted by the liver on osteogenic differentiation in MAFLD.METHODS RNA sequencing was performed to identify highly expressed circRNAs in the liver,validated by quantitative real-time reverse transcription polymerase chain reaction,and localized using fluorescence in situ hybridization(FISH).A mouse model induced by a high-fat diet was used to simulate MAFLD.RESULTS CircSOD2 was significantly upregulated in liver tissues and primary hepatocytes from subjects with MAFLD.CircSOD2 was induced by oxidative stress and attenuated by antioxidants in the mouse model.In addition,circSOD2 was delivered from hepatocytes to bone marrow mesenchymal stem cells(BMSCs).Furthermore,circSOD2 inhibited the osteogenic differentiation of BMSCs and in vivo bone formation by sponging miR-29b.Moreover,miR-29b inhibition reversed the stimulatory effect of circSOD2 silencing on osteogenic differentiation of BMSCs and in vivo bone formation.Mechanistically,the interaction between circSOD2 and miR-29b confirmed through a luciferase reporter assay and the co-localization in the cytoplasm evidenced by FISH indicated that circSOD2 acted as a sponge for miR-29b.CONCLUSION This study provides a novel mechanism underlying the liver-bone crosstalk,demonstrating that circSOD2 upregulation in hepatocytes,induced by oxidative stress,inhibits osteogenic differentiation of BMSCs by sponging miR-29b.These findings offer a better understanding of the relationship between MAFLD and osteoporosis.
基金supported by central government-guided major science and technology project of Hebei province 236Z7709G(M.C.Q.)Tangshan science and technology project 23130216E(M.C.Q.)+8 种基金key research projects of North China University of Science and Technology ZD-YG-202309(M.C.Q.)National Natural Science Foundations of China 82230030 and 81871492(Y.L.)Beijing International Science and Technology Cooperation Project Z221100002722003(Y.L.)Beijing Natural Science Foundation L234017(Y.L.)Peking University Medicine plus X Pilot Program-Key Technologies R&D Project 2024YXXLHGG004(Y.L.)Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)First-Class Discipline Team of Kunming Medical University 2024XKTDTS08(Y.L.)Innovative Research Team of High-level Local Universities in Shanghai SHSMU-ZLCX20212402(Y.L.)Postdoctoral Fellowship Program of CPSF under Grant Number GZB20240038(X.J.C.).
文摘Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.
基金supported by the National Natural Science Foundation of China(51972339,52072023,and 51802350)the National Natural Science Found for Distinguished Young Scholars(52225101)+3 种基金the China Postdoctoral Science Foundation(2022M720551)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0527,cstc2021jcyj-msxmX0993)the Chongqing Academician Special Fund(2022YSZX-JCX0014CSTB)the Chongqing Science and Technology Commission(CSTB2022NSCQ-MSX0416).
文摘Magnesium(Mg)alloys with biodegradability and excellent mechanical properties are in high demand for applications in guided bone regeneration(GBR).However,the clinical application of Mg alloys is hindered by infection risks and limited osteogenesis.Herein,a structure-functional integrated Mg-Ca/Mg-Cu bilayer membrane was rolled at 150℃through various single-pass reductions by using online heating rolling.The Mg-Cu layer was specifically engineered to exhibit antibacterial properties tailored for gingival tissue,while the Mg-Ca layer was designed to support bone regeneration within the defect cavity.The bilayer membrane demonstrated a flexural yield strength of 421.0 MPa and a modulus of 58.6 GPa,indicating exceptional deformation resistance.Furthermore,it maintained notable structural stability by retaining 86.4%of its volume after 21 days in Hanks'solution.In vitro results revealed that the bilayer membrane exhibited favorable biocompatibility and promoted osteogenesis via the synergetic effect of released Mg^(2+)and Ca^(2+)ions.The rapid release of Cu^(2+)ions and the creation of an alkaline environment further improved antibacterial properties,potentially preventing postoperative infections.Additionally,in an in vivo rat calvarial defect model,the membrane demonstrated its capability to stimulate new bone formation.In summary,the Mg-Ca/Mg-Cu bilayer membrane exhibited outstanding mechanical stability,favorable corrosion rates,extraordinary osteogenic and antibacterial activity simultaneously.Consequently,it holds promise as a robust barrier membrane in GBR applications.
基金supported by the National Key Research and Development Program of China(2021YFC2400700)the National Science Foundation of China(82370924,82170929)+5 种基金the Beijing Natural Science Foundation Haidian Original Innovation Joint Fund Project(L222090)the Fujian Province Natural Science Foundation of China(2021J01803)the Postdoctoral Fellowship Program of 5CPSF(GZC20230141)the Beijing Municipal Natural Science Foundation-Changping Innovation Joint Fund Project(L234074)Industry-University-Research Innovation Fund for Chinese Universities(2024GR021)the Innovation research program(HHKT-00-03).
文摘Guided bone regeneration(GBR)membranes are extensively utilized in dental implantation.However,the existing GBR membranes showed insufficient space-maintaining capability and poor bone promoting ability,affecting the effectiveness of clinical bone augmentation,which in turn resulted in poor implant outcomes and even failure.In this study,we designed a novel magnesium reinforced sandwich structured composite membrane,consisting of an inner magnesium scaffold and a PLGA/collagen hybrid(mixture of poly(lactic-co-glycolic acid)and collagen)top and bottom layer.The magnesium scaffold provided mechanical support and released Mg^(2+)to enhance osteogenesis.The PLGA/collagen hybrid regulated membrane degradation and improved biocompatibility,promoting cell adhesion and proliferation(P<0.05).The PLGA/collagen hybrid regulated the release of magnesium ions,such that the MgP10C(mass ratios of PLGA and collagen=100:10)group showed the best in vitro osteogenic effect.Further mechanism exploration confirmed that MgP10C membranes significantly enhanced bone defect repair via the MAPK/ERK 1/2 pathway by the Mg^(2+)released from the composite membranes.In rat calvarial defect and rabbit alveolar defect model(P<0.05),the in vivo osteogenic effect of the MgP10C group was superior to that of other groups.Finite element analysis models validated the support effect of composite membranes,demonstrating lower stress and a significant reduction in strain on the bone graft in the MgP10C group.In conclusion,the magnesium-reinforced sandwich structure composite membrane,with its spacemaintaining properties and osteoinductive activity,represents a new strategy for GBR and enhancing osteogenic potential that meets directly clinical needs.
基金supported by the National Natural Science Foundation of China(Nos.52072127,52201297,U21A2055,and U22A20160)the China Postdoctoral Science Foundation(No.2022M711200)the Royal Society(No.IEC/NSFC/191344)(UK).
文摘Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration when designing biomedical implants. In this research, ordered structures with Schottky heterojunction functional unit (OSSH) were constructed on titanium implant surfaces for bone regeneration regulation. The Schottky heterojunction functional unit is composed of periodically distributed titanium microdomain and titanium oxide microdomain with different carrier densities and surface potentials. The OSSH regulates the M2-type polarization of macrophages to a regenerative immune response by activating the PI3K-AKT-mTOR signal pathway and further promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells. This work provides fundamental insights into the biological effects driven by the Schottky heterojunction functional units that can electrically modulate osteogenesis.
基金supported by the National Natural Science Foundation of China(No.81901430)the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010379)+1 种基金the Science and Technology Projects in Guangzhou(No.2023A04J0555)the Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion(No.2021B1212040014),China.
文摘Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,the additional functions of the bone vasculature,such as the secretion of various factors and the regulation of bone-related signaling pathways,are essential for maintaining bone health.In the bone microenvironment,bone tissue cells play a critical role in regulating angiogenesis,including osteoblasts,bone marrow mesenchymal stem cells(BMSCs),and osteoclasts.Osteogenesis and bone angiogenesis are closely linked.The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis.Long noncoding RNAs(lncRNAs)are involved in various physiological processes,including osteogenesis and angiogenesis.Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis.However,the mechanism by which lncRNAs regulate angiogenesis-osteogenesis crosstalk remains unclear.In this review,we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health,aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
基金support from the National Institute of Health(K99AR081897,R00AR081897)M.N.W.acknowledges funding support from the National Institute of Health(P01DK011794,R01DK116716)+1 种基金the Smith Family Foundation Odyssey Award,and the Chen Institute Massachusetts General Hospital Research Scholar(2024-2029)awardμCT and bone histomorphometry were performed by the Center for Skeletal Research at Massachusetts General Hospital,a NIH-funded program(P30AR066261 and AR075042)led by Mary Bouxsein and Marie Demay).
文摘Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role of matrix-embedded osteocytes in OI pathogenesis remains largely unknown.Homozygous human SP7(c.946 C>T,R316C)mutation results in a recessive form of OI characterized by fragility fractures,low bone mineral density and osteocyte dendrite defects.To better understand how the OI-causing R316C mutation affects the function of SP7,we generated Sp7^(R342C)knock-in mice.Consistent with patient phenotypes,Sp7^(R342C/R342C)mice demonstrate increased cortical porosity and reduced cortical bone mineral density.Sp7^(R342C/R342C)mice show osteocyte dendrite defects,increased osteocyte apoptosis,and intracortical bone remodeling with ectopic intracortical osteoclasts and elevated osteocyte Tnfsf11 expression.
基金Supported by National Natural Science Foundation of China,No.82072425.
文摘BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.
基金supported by National Natural Science Foundation of China(nos.52071346,52111530193)the Natural Science Foundation of Hunan Province for Distinguished Young Scholars(2023JJ10075)+3 种基金Hunan Provincial Natural Science Foundation of China(2021JJ30846)Natural Science Foundation of Hunan Province(2023JJ40836)Central South University Research Program of Advanced Interdisciplinary Studies(2023QYJC038)Fundamental Research Funds for the Central Universities of Central South University(2022ZZTS0402).
文摘Magnesium(Mg)and its alloys have similar densities and elastic moduli to natural bone,making them an excellent choice for orthopedic implants.However,Mg alloys are prone to electrochemical corrosion,which often leads to implant failure and hinders the further development of Mg alloys due to bacterial infection around the implant.This work aims to enhance the corrosion resistance of Mg alloys,and provide theoretical guidance for solving the problem that Mg-based orthopedic implants are susceptible to bacterial infection and,thus,implant failure.In order to solve the corrosion problem,the Mg alloy AZ91D was used as the substrate,and a compact and uniform MgAlCu-layered double hydroxide(Mg(Cu)-LDH)was prepared on its surface using a hydrothermal method.The Mg(Cu)-LDH provides a barrier between the AZ91D and corrosive liquid,which effectively protects the Mg substrate from being corroded.The Mg(Cu)-LDH shows great cell viability for MC3T3-E1 cells.The Cu^(2+)and Mg^(2+) in the coating also endow the Mg(Cu)-LDH/AZ91D with antibacterial properties,showing strong antibacterial effects on both E.coli and S.aureus with antibacterial rates over 85%.Finally,in vivo results indicated that a LDH-coated implant had no systemic effects on the hearts,livers,spleens,lungs or kidneys.It was shown that 4 weeks after surgery the ratio of bone volume to tissue volume(BV/TV)of the LDH implant was 24%,which was 1.7 times that observed for AZ91D.
基金supported by The National Key Research and Development Program of China(No.2020YFC1107501)National Natural Science Foundation of China(No.51971222),STS program(No.20201600200042)Dong Guan Innovative Research Team Program.Basic applied research program of Liaoning Province of China(No.2022020347-JH2/1013)。
文摘Biodegradable magnesium-matrix composites(BMMCs)added with bone-like compounds such as hydroxyapatite(HA)have promising orthopedic application potential,but the in vivo results of BMMCs are insufficient,and the difference between in vitro and in vivo are not clarified.In this work,Mg-Zn-Nd-Zr/(10/15/20wt%)HA(Ca_(10)(PO_(4))_(6)OH_(2))composites were prepared through friction stirring processing(FSP).It was found that corrosion rate of the composites increased with increase of the HA content,where the corrosion rate from hydrogen evolution of the Mg/10wt%HA was about 0.107 mm/y,showing better corrosion resistance compared with other BMMCs,and the agglomeration of HA powders significantly aggravated the localized corrosion.The ALP specific activity of the MC3T3-E1 cells cultured for14 days with Mg/10wt%HA(2.12 IU/mg)was higher than that of the matrix(1.85 IU/mg),but there was no difference with the FSP group(2.13 IU/mg).In the early implantation of the rabbit femur,bone volume fraction(BV/TV)of Mg/10wt%HA was 10.69,which was higher than that of the FSP group(6.35).The histological staining showed that the Mg/10wt%HA implant was surrounded by more trabecular bone tissue,exhibiting better osteoinductive regeneration.The Mg-Zn-Nd-Zr/HA composites exhibit higher osteogenic activity in vivo differently from in vitro osteogenic expression.
文摘Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed through genetic studies. We present a case of osteogenesis imperfecta suspected during obstetrical ultrasound at 19 weeks’ gestation, which was later confirmed radiographically through computed tomography. Due to the severity of the condition, therapeutic termination of pregnancy was indicated.
基金supported by grants from the National Nature Science Foundation of China (No. 30772454)Science and Technology Bureau of Sichuan Province (No. 2006z09-013)
文摘Aim Understanding the response of mesenchymal stem cells （MSCs） to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis. Methodology In this study, a single period of cyclic mechanical stretch （0.5 Hz, 2,000 με） was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase （ALP） activity was examined. The mRNA expression of six bone-related genes （Ets-1, bFGF, IGF-Ⅱ, TGF-β, Cbfal and ALP） was detected using real-time quantitative RT-PCR. Results The results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfal expression became elevated later. The temporal expression pattem of ALP coincided perfectly with Cbfal. Conclusion The results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts, and that these bone-related genes may play different roles in the response of MSCs to mechanical stimulation.
基金financially supported by National Natural Science Foundation of China (81100240)‘985’ project of Sun Yat-Sen University grant+2 种基金Sun Yat-Sen university young teachers training project (13YKPY42)Natural Science Foundation of Guangdong Province,China(S2012010009495)Science and Technology Planning Project of Guangdong Province,China(2012B031800185)
文摘Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.
基金Project (No. 20070421123) supported by the Postdoctoral Science Foundation of China
文摘Objective： We investigated the effects of intermittent negative pressure on osteogenesis in human bone marrowderived stroma cells （BMSCs） in vitro. Methods： BMSCs were isolated from adult marrow donated by a hip osteoarthritis patient with prosthetic replacement and cultured in vitro. The third passage cells were divided into negative pressure treatment group and control group. The treatment group was induced by negative pressure intermittently （pressure： 50 kPa, 30 min/times, and twice daily）. The control was cultured in conventional condition. The osteogenesis of BMSCs was examined by phase-contrast mi- croscopy, the determination of alkaline phosphatase （ALP） activities, and the immunohistochemistry of collagen type 1. The mRNA expressions of osteoprotegerin （OPG） and osteoprotegerin ligand （OPGL） in BMSCs were analyzed by real-time polymerase chain reaction （PCR）. Results： BMSCs showed a typical appearance of osteoblast after 2 weeks of induction by intermittent negative pressure, the activity of ALP increased significantly, and the expression of collagen type I was positive. In the treatment group, the mRNA expression of OPG increased significantly （P〈0.05） and the mRNA expression of OPGL decreased significantly （P〈0.05） after 2 weeks, compared with the control. Conclusion： Intermittent negative pressure could promote osteogenesis in human BMSCs in vitro.
基金supported in part by grants from the National Institutes of Health(AG051773)and VA(BX000838)
文摘YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.
基金supported by National Natural Science Foundation of China (81600828)Shanghai Sailing Program (16YF1406600)
文摘Ginsenoside Rb1, the effective constituent of ginseng, has been demonstrated to play favorable roles in improving the immunity system. However, there is little study on the osteogenesis and angiogenesis effect of Ginsenoside Rb1. Moreover, how to establish a delivery system of Ginsenoside Rb1 and its repairment ability in bone defect remains elusive. In this study, the role of Ginsenoside Rb1 in cell viability, proliferation, apoptosis, osteogenic genes expression, ALP activity of rat BMSCs were evaluated firstly. Then,micro-nano HAp granules combined with silk were prepared to establish a delivery system of Ginsenoside Rb1, and the osteogenic and angiogenic effect of Ginsenoside Rb1 loaded on micro-nano HAp/silk in rat calvarial defect models were assessed by sequential fluorescence labeling, and histology analysis, respectively. It revealed that Ginsenoside Rb1 could maintain cell viability, significantly increased ALP activity, osteogenic and angiogenic genes expression. Meanwhile, micro-nano HAp granules combined with silk were fabricated smoothly and were a delivery carrier for Ginsenoside Rb1. Significantly, Ginsenoside Rb1 loaded on micro-nano HAp/silk could facilitate osteogenesis and angiogenesis. All the outcomes hint that Ginsenoside Rb1 could reinforce the osteogenesis differentiation and angiogenesis factor’s expression of BMSCs. Moreover, micro-nano HAp combined with silk could act as a carrier for Ginsenoside Rb1 to repair bone defect.
基金a grant from the National Natural Sciences Foundation of China (No. 50477043)
文摘In order to identify the differentially expressing gene of bone marrow mesenchymal stem cells （MSCs） stimulated by electromagnetic field （EMF） with osteogenesis microarray analysis, the bone marrow MSCs of SD rats were isolated and cultured in vitro. The third-passage cells were stimulated by EMFs and total RNA was extracted, purified and then used for the synthesis of cDNA and cRNA. The cRNA of stimulated group and the control group was hybridized with the rat oligo osteogenesis microarray respectively. The hybridization signals were acquired by using X-ray film after chemiluminescent detection and the data obtained were analyzed by employing the web-based completely integrated GEArray Expression Analysis Suite. RT-PCR was used to identify the target genes： Bmp1, Bmp7, Egf and Egfr. The results showed that 19 differentially expressing genes were found between the stimulated group and the control group. There were 6 up-regulated genes and 13 down-regulated genes in the stimulated group. Semi-quantitative RT-PCR confirmed that the expressions of Bmpl, Bmp7 mRNA of the stimulated group were up-regulated （P〈0.05） and those of Egf, Egfr were down-regulated （P〈0.05）. It was suggested that the gene expression profiles of osteogenesis of the bone marrow MSCs were changed after EMF treatment. It is concluded that the genes are involved in skeletal development, bone mineral metabolism, cell growth and differentiation, cell adhesion etc.
基金funded by National Natural Science Foundation of China (81071273,31170929)Foundation for the Author of National Excellent Doctoral Dissertation of China (FANEDD 200977)Innovative Research Team of Education Department of Sichuan Province (13TD0038)
文摘Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.
基金supported by a grant from the ITI International Team for Implantology Foundation 1235_2017 to M.B.A
文摘Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P <0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.
