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| 1 | Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms显示文摘Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients. | Kannikar Wongdee Narattaphol Charoenphandhu | 2011 | World Journal of Diabetes2011，2，3： | 51 |
| 2 | RANKL,a necessary chance for clinical application to osteoporosis and cancer-related bone diseases显示文摘Osteoporosis is a common bone disease characterized by reduced bone and increased risk of fracture. In postmenopausal women, osteoporosis results from bone loss attributable to estrogen deficiency. Osteoclast differentiation and activation is mediated by receptor activator of nuclear factor-κB ligand(RANKL), its receptor receptor activator of nuclear factor-κB(RANK), and a decoy receptor for RANKL, osteoprotegerin(OPG). The OPG/RANKL/RANK system plays a pivotal role in osteoclast biology. Currently, a fully human antiRANKL monoclonal antibody named denosumab is being clinically used for the treatment of osteoporosis and cancer-related bone disorders. This review describes recent advances in RANKL-related research, a story from bench to bedside. First, the discovery of the key factors, OPG/RANKL/RANK, revealed the molecular mechanism of osteoclastogenesis. Second, we established three animal models:(1) a novel and rapid bone loss model by administration of glutathione-S transferase-RANKL fusion protein to mice;(2) a novel mouse model of hypercalcemia with anorexia by overexpression of soluble RANKL using an adenovirus vector; and(3) a novel mouse model of osteopetrosis by administration of a denosumab-like anti-mouse RANKL neutralizing monoclonal antibody. Lastly, anti-human RANKL monoclonal antibody has been successfully applied to the treatment of osteoporosis and cancer-related bone disorders in many countries. This is a real example of applying basic science to clinical practice. | Hisataka Yasuda | 2013 | World Journal of Orthopedics2013，4，4： | 22 |
| 3 | Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro显示文摘The present study aimed at investigating the effects of Puerarin(PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized(OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR(2, 4, and 8 mg·d^(-1), respectively) or 17β-estradiol(E_2, 0.03 μg·d^(-1)) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density(BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase(TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand(RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin(OPG) and RANKL m RNA expression in osteoblasts. The expression of OPG m RNA and RANKL m RNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG m RNA and reduced the expression of RANKL m RNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts. | YUAN Si-Yuan SHENG Tong LIU Lian-Qi ZHANG Yun-Ling LIU Xue-Mei MA Tao ZHENG Hong YAN Yan ISHIMI Yoshiko WANG Xin-Xiang | 2016 | Chinese Journal of Natural Medicines2016，14，4： | 20 |
| 4 | The proliferation, differentiation, and mineralization effects of puerarin on osteoblasts in vitro显示文摘AIM: Osteoblasts are key functional cells in the process of bone metabolic balance. Phytoestrogens have an important influence on the proliferation and differentiation of osteoblasts. Puerarin, a plant estrogen, has a wide range concentration in vitro on the function of osteoblasts. The current study investigates the effect of the phytoestrogen puerarin on the proliferation, differentiation, and mineralization of osteoblasts in vitro. METHODS: The calvaria bone of eight-ten Wistar rats which were born within 24 h were obtained in aseptic condition. After enzyme digestion, isolation, purified osteoblasts of rats were cultured for further study. The cells of the first to third generation were divided into a control group and a puerarin-treated group with 10-3–10-10 mol·L-1 puerarin. The cells were exposed to the medium containing a low level of carbohydrates, 10%(V/V) FBS for 24 h. After 1 to 4 days of culture, the OD values on the proliferation of osteoblasts in each group were determined by microplate reader. The cells were cultured in the medium containing 50 μg·mL-1 vitamin C, 10-2 mol·L-1 sodium glycerophosphate, 10% FBS and the medium was changed every 3 to 4 days. After 2 to 8 days of culture, expression of alkaline phosphatase were tested and compared by microplate reader. The mineral nodes of osteoblasts were dyed using alizarin red or improved Von Kossa way after four weeks. RESULTS: Compared with those in the 10-5–10-9 mol·L-1 puerarin, the proliferation of osteoblasts, the expression of alkaline phosphatase, and the number of mineral nodes of osteoblasts were significantly decreased in the control group. The increase was the fastest in the third day, while on the fourth day it was decreased, and arrived at statistical significance compared with the alkaline phosphatase activities and control group. The 10-6 mol·L-1 group was the most distinct, and formed the most mineralized nodule. Compared with the 10-3 mol·L-1 puerarin group, those changes were markedly increased in the control group. CONCLUSIONS: Puerarin has proliferation, differentiation, and mineralization effects on osteoblasts in a dose-dependent manner, and has a double-way effect on the osteoblasts in vitro. A low-dose showed positive effects on the development of osteoblasts, and high-dose puerarin could inhibit the formation of bone. | WANG Chang MENG Mei-Xia TANG Xu-Lei CHEN Ke-Ming ZHANG Li LIU Wei-Ning ZHAO Ying-Yong | 2014 | Chinese Journal of Natural Medicines2014，12，6： | 18 |
| 5 | New roles of osteoblasts involved in osteoclast differentiation显示文摘Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF,RANKL,and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34(IL-34)a novel ligand for c-Fms,plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a,produced by osteoblasts,enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus,recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases. | Teruhito Yamashita Naoyuki Takahashi Nobuyuki Udagawa | 2012 | World Journal of Orthopedics2012，3，11： | 11 |
| 6 | Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway显示文摘Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses.Additionally,the NLRP3 inflammasome is activated by prosthetic particles.Sirtuin3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse activities.However,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported.Therefore,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced osteolysis.We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro.Moreover,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway.Collectively,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation. | Kai Zheng Jiaxiang Bai Ning Li Meng Li Houyi Sun Weicheng Zhang Gaoran Ge Xiaolong Liang Huaqiang Tao Yi Xue Yuefeng Hao Chen Zhu Yaozeng Xu Dechun Geng | 2021 | Bioactive Materials2021，6，10： | 5 |
| 7 | Increased Expression of Receptor Activator of Nuclear Factor-κB Ligand in Osteoblasts from Adolescent Idiopathic Scoliosis Patients with Low Bone Mineral Density显示文摘Persistent generalized low bone mineral density (BMD) has been reported in patients with adolescent idiopathic scoliosis (AIS).However,the exact mechanisms and causes of the low BMD in AIS patients are largely unknown.The purpose of this study was to examine the relationship between the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) levels in osteoblasts (OBs) from AIS patients with low BMD and with comparison made between the patients and controls.Twenty AIS patients and eight age-matched controls were included in the present study.The BMD of lumbar spine and proximal femur was measured in all subjects.OBs from the cancellous bone of each subject was harvested and primarily cultured.The mRNA and protein expression of RANKL and OPG in OBs was detected by RT-PCR and Western blotting.The results showed BMD was lower in AIS patients than in controls.A significantly higher mRNA and protein expression of RANKL was observed in OBs from AIS patients,while no significant difference was found in the expression of OPG between AIS patients and controls.As a result,RANKL/OPG ratio in patients with AIS was remarkably higher than controls.Our study preliminarily demonstrated expression of RANKL was higher in OBs from AIS patients with low BMD as compared with controls,suggesting the unbalanced RANKL/OPG ratio caused by an over-expression of RANKL in OBs may be responsible for the low BMD in AIS patients. | 周松 王渭君 朱泽章 孙旭 朱锋 俞杨 钱邦平 王斌 殷刚 邱勇 | 2012 | Journal of Huazhong University of Science and Technology(Medical Sciences)2012，32，5： | 4 |
| 8 | Smart biomaterials: Surfaces functionalized with proteolytically stable osteoblast-adhesive peptides显示文摘Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion,growth,proliferation and differentiation.Recently,covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide(HVP)mapped on[351e359]sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays,and to promote osseointegration in in vivo studies.For the first time to our knowledge,in this study we investigated the resistance of adhesion sequences to proteolytic digestion:HVP was completely cleaved after 5 h.In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence.A retro-inverted peptide D-2HVP,composed of D amino acids,was completely stable in serum-containing medium.In addition,glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium.Interestingly,D-2HVP increased expression of IBSP,VTN and SPP1 genes as compared to HVP functionalized surfaces.Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces.Therefore,the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance. | Annj Zamuner Paola Brun Michele Scorzeto Giuseppe Sica Ignazio Castagliuolo Monica Dettin | 2017 | Bioactive Materials2017，2，3： | 3 |
| 9 | MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation显示文摘Granted by the National Science Foundation for Distinguished Young Scholars of China,Prof.Luo Xianghang’s team from the Institute of Endocrinology and Metabolism,Second Xiangya Hospital,Central South University,reported that microRNA-188regulates age-related switch between osteoblast and adipocyte differentiation.Their work has been published in J Clin Invest(2015,125(4):1509—22). | | 2015 | Science Foundation in China2015，23，4： | 3 |
| 10 | Review for treatment and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis显示文摘The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. | Ya-ping XIAO Jie ZENG Lin-na JIAO Xiao-yu XU | 2017 | 中国药理学与毒理学杂志2017，31，10： | 3 |
| 11 | New Insights into the Molecular Basis of Kidney Governing Bone Theory显示文摘Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine(TCM). However, the exact biological basis of kidney governing bone theory in the context of new advances in biology is still not fully established. In this paper, the content of kidney governing bone theory in biology has been fully demonstrated from different aspects. We first propose that bone and kidney mutually affect each other in pathology and physiology, particularly through homeostasis of calcium, phosphorus and fibroblast growth factor-23(FGF-23). Next, we identify that tonifying kidney prescriptions/herbs exert bone protective effects, thus treating osteoporosis by regulating bone formation and bone resorption.Furthermore, the exact molecular mechanisms of tonifying kidney prescriptions, herbs and their effective components in treating osteoporosis have been systematically reviewed. Finally, we come into the conclusion that kidney regulating bone mineral homeostasis, bone protective effects of tonifying kidney herbs and regulatory effects on bone homeostasis are all the manifestations of kidney governing bone theory.Therefore, the new insights into kidney governing bone theory in biology will promote the development of clinical practices, and drugs discovery in treating osteoporosis. | Dong-feng Zhao Yong-jian Zhao Cheng-long Wang Yan-ping Yang Yong-jun Wang | 2015 | World Journal of Traditional Chinese Medicine2015，1，3： | 2 |
| 12 | Osteoblast behaviors on titania nanotube and mesopore layers显示文摘Titania nanotubes and mesopores with different diameter sizes were prepared by electrochemical oxidation of titanium.The responses of osteoblastic cells isolated from Sprague–Dawley rats to the nanotube and mesopore layers were investigated in sequential events of cell adhesion,morphology,actin cytoskeleton,proliferation,differentiation,and mineralization.Nano-structural features,especially diameters of the nanotubes and mesopores,obviously influenced on cell behaviors in the sequential events.The cells showed better proliferation and differentiation abilities on the specimens with the nanotubes and mesopores than on flat titanium disk.Higher levers of calcium mineralization were observed on the nanotube and mesopore layers.The cells adhered much faster onto the nanotubes with about 170nm diameter and the mesopores with about 400nm diameter than onto flat titanium disk and 50nm nanotubes.There is an appropriate range of the tube/pore sizes,and in this present work,titania nantubes with 170nm diameter is the best for enhancing functions of osteoblasts. | Yan Zhang Rong Luo Jing Tan Jianxin Wang Xiong Lu Shuxin Qu Jie Weng Bo Feng | 2017 | Regenerative Biomaterials2017，4，2： | 2 |
| 13 | Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation显示文摘Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response.Interleukin(IL)-17A,produced in the early phase of inflammation,influences the fate of osteoprogenitors.Due to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and regeneration.This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs.The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described.To this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell types.Therefore,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration. | Jelena Krstić Slavko Mojsilović Sonja S Mojsilović Juan F Santibanez | 2021 | World Journal of Stem Cells2021，13，11： | 2 |
| 14 | Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition显示文摘The imbalance of bone homeostasis is the root cause of osteoporosis.However current therapeutic approaches mainly focus on either anabolic or catabolic pathways,which often fail to turn the imbalanced bone metabolism around.Herein we reported that a SIRT-1 agonist mediated molecular therapeutic strategy to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis via locally sustained release of SRT2104 from mineral coated acellular matrix microparticles.Immobilization of SRT2104 on mineral coating(MAM/SRT)harnessing their electrostatic interactions resulted in sustained release of SIRT-1 agonist for over 30 days.MAM/SRT not only enhanced osteogenic differentiation and mineralization,but also attenuated the formation and function of excessive osteoclasts via integrating multiple vital upstream signals(β-catenin,FoxOs,Runx2,NFATc1,etc.)in vitro.Osteoporosis animal model also validated that it accelerated osteoporotic bone healing and improved osseointegration of the surrounding bone.Overall,our work proposes a promising strategy to treat osteoporotic bone defects by reversing the imbalance in bone homeostasis using designated small molecule drug delivery systems. | Wei Zhang Xingzhi Zhou Weiduo Hou Erman Chen Chenyi Ye Mo Chen Qian Lu Xiaohua Yu Weixu Li | 2023 | Bioactive Materials2023，，1： | 2 |
| 15 | Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro显示文摘Hypertension is a prevalent systemic disease in the elderly,who can suffer from several pathological skeletal conditions simultaneously,including osteoporosis.Benidipine(BD),which is widely used to treat hypertension,has been proved to have a beneficial effect on bone metabolism.In order to confirm the osteogenic effects of BD,we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro.The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD,as measured by methylthiazolyldiphenyl-tetrazolium bromide(MTT)assay and cell cycle assay.With BD treatment,the osteogenic differentiation and maturation of MC3T3-E1 cells were increased,as established by the alkaline phosphatase(ALP)activity test,matrix mineralized nodules formation,osteogenic genetic test,and protein expression analyses.Moreover,our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD,while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK(receptor activator of nuclear factor-κB(NF-κB))pathway.The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study. | Baixiang WANG Jiakang YANG Lijie FAN YuWANG Chenqiu ZHANG HuimingWANG | 2021 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2021，22，5： | 2 |
| 16 | Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells显示文摘Objective To observe the expression profiles of osteoblast-related genes in human mesenchymal stem cells(MSCs) derived from bone marrow during osteogenic differentiation. Methods MSCs were induced to differentiate with MSC osteogenic differentiation medium for 7, 14, 21 and 28 days respectively. Alizarin Red staining was used to detect matrix mineralization. Expression of osteoblast-related genes, including osteocalcin, osteopontin, Runt-related transcription factor 2(Runx2), alkaline phosphatase and collagen type Ⅰ, was assessed with quantitative reverse transcription-polymerase chain reaction. Results On day 14 after induction of differentiation, cells were stained positively with Alizarin Red. The expression levels of these genes exhibited an upward trend as induction time was prolonged. Exposure to osteogenic differentiation medium less than 21 days did not significantly induce osteocalcin expression; osteocalcin expression levels in the differentiated cells induced for 21 and 28 days were 1.63 and 2.46 times as high as the undifferentiated cells respectively(all P<0.05). Stimulation with MSC osteogenic differentiation medium over 14 days significantly enhanced bone marrow-derived MSCs to express osteopontin and Runx2 genes(all P<0.05). Osteogenic differentiation medium could significantly induce the expressions of alkaline phosphatase and collagen type Ⅰgenes(all P<0.05). Their expressions reached the peak levels on day 21, which were increased more than 4- and 3-fold respectively. Conclusion Human bone marrow-derived MSCs could exhibit the sequential expression pattern of osteoblast marker genes during osteogenic differentiation in vitro. | Liang Wang Zheng-yao Li Yi-peng Wang Zhi-hong Wu Bin Yu | 2015 | Chinese Medical Sciences Journal2015，30，2： | 2 |
| 17 | E26 transformation-specific 1 is implicated in the inhibition of osteogenic differentiation induced by chronic high glucose by directly regulating Runx2 expression显示文摘Chronic high glucose(HG) plays a crucial role in the pathogenesis of diabetes-induced osteoporosis by inhibiting the differentiation and proliferation of osteoblasts. This study aims to examine the role of E26 transformation-specific 1(ETS1) in the inhibition of osteoblast differentiation and proliferation caused by chronic HG, as well as the underlying mechanism. Chronic HG treatment downregulated ETS1 expression and inhibited differentiation and proliferation of MC3 T3-E1 cells. Downregulation of ETS1 expression inhibited the differentiation and proliferation of MC3 T3-E1 cells under normal glucose conditions, and ETS1 overexpression attenuated the damage to cells exposed to chronic HG. In addition, ETS1 overexpression reversed the decrease in runt-related transcription factor 2(Runx2) expression in MC3 T3-E1 cells treated with chronic HG. Using chromatin immunoprecipitation(ChIP) and luciferase reporter assays, we confirmed that ETS1 directly bound to and increased the activity of the Runx2 promoter. In summary, our study suggested that ETS1 was involved in the inhibitory effect of chronic HG on osteogenic differentiation and proliferation and may be a potential therapeutic target for diabetes-induced osteoporosis. | Wenqian Xia Xiao Han Lin Wang | 2022 | The Journal of Biomedical Research2022，36，1： | 2 |
| 18 | Effect of High Positive Acceleration(+Gz) Environment on Dental Implant Osseointegration:A Preliminary Animal Study显示文摘Objective To observe the effect of high positive acceleration(+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism.Methods Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit’s mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks(2 weeks +Gz exposure), 5 weeks(4 weeks +Gz exposure), and 12 weeks(4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination.Results Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2(BMP-2), osteopontin(OPN), and transforming growth factor-β1(TGF-β1)were significantly lower(P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand(RANKL) and the RANKL/osteoprotegerin(OPG) ratio were significantly higher(P < 0.05)at 3 weeks;values of bone volume fraction, trabecular number, bone-implant contact(BIC), and TGF-β1 and OPG mRNA expression levels were significantly lower(P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher(P < 0.05) at 5 weeks;and the value of BIC was still significantly lower(P < 0.05) at 12 weeks in the experimental group.Conclusion Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity. | ZHU Xiao Ru DENG Tian Zheng PANG Jian Liang LIU Bing KE Jie | 2019 | Biomedical and Environmental Sciences2019，32，9： | 1 |
| 19 | Decarboxylated osteocalcin,a possible drug for type 2 diabetes,triggers glucose uptake in MG63 cells显示文摘BACKGROUND Uncarboxylated osteocalcin(GluOC)has been reported to improve glucose metabolism,prevent type 2 diabetes,and decrease the severity of obesity in mice with type 2 diabetes.GluOC can increase glucose uptake in a variety of cells.Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation.We hypothesized that decarboxylated osteocalcin(dcOC),a kind of GluOC,can increase glucose uptake in MG63 cells(osteoblast-like osteosarcoma cells)and influence their proliferation and differentiation.AIM To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved.METHODS MG63 cells(human osteoblast-like osteosarcoma cells)were treated with dcOC(0,0.3,3,10,or 30 ng/mL)for 1 and 72 h,and glucose uptake was measured by flow cytometry.The effect of dcOC on cell proliferation was measured with a CCK-8 assay,and alkaline phosphatase(ALP)enzyme activity was measured.PI3K was inhibited with LY294002,and hypoxia-inducible factor 1 alpha(HIF-1α)was silenced with siRNA.Then,GPRC6A(G protein-coupled receptor family C group 6 subtype A),total Akt,phosphorylated Akt,HIF-1α,and glucose transporter 1(GLUT1)levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake.RESULTS The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term(1 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term(72 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).DcOC triggered Akt phosphorylation in a dose-dependent manner,and the most effective stimulatory concentration of dcOC for short-term(1 h)was 3 ng/mL(P<0.01).LY294002 abolished the dcOC-mediated(1 h)promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression.Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α,GLUT1,and Runx2 in a dose-dependent manner.Inhibition of HIF-1αwith siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression.DcOC interven-tion promoted cell proliferation in a time-and dose-dependent manner as determined by the CCK-8 assay.Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h(P<0.01).CONCLUSION Short-and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells.This effect may occur through the PI3K/Akt,HIF-1α,and GLUT1 signaling factors. | Shi Jin Xiao-Cen Chang Jing Wen Jing Yang Na Ao Ke-Ying Zhang Lin-Na Suo Jian Du | 2021 | World Journal of Diabetes2021，12，7： | 1 |
| 20 | Nystose attenuates bone loss and promotes BMSCs differentiation to osteoblasts through BMP and Wnt/β-catenin pathway in ovariectomized mice显示文摘Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells(BMSCs)is a potential strategy for the treatment of osteoporosis(OP).Naturally derived oligosaccharides have shown significant anti-osteoporotic effects.Nystose(NST),an oligosaccharide,was isolated from the roots of Morinda officinalis How.(MO).The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice,and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts.Administration of NST(40,80 and 160 mg/kg)and the positive control of estradiol valerate(0.2 mg/kg)for 8 weeks significantly prevented bone loss induced by ovariectomy(OVX),increased the bone mass density(BMD),improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline(DPD)in ovariectomized mice,while inhibited the increase of body weight without significantly affecting the uterus weight.Furthermore,we found that NST increased osteogenic differentiation,inhibited adipogenic differentiation of BMSCs in vitro,and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways.In addition,Noggin and Dickkopf-related protein-1(DKK-1)reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway.The luciferase activities and the molecular docking analysis further supported the mechanism of NST.In conclusion,these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis. | Qi Zhang Sijing Hu Jianjun Wu Peng Sun Quanlong Zhang Yang Wang Qiming Zhao Ting Han Luping Qin Qiaoyan Zhang | 2023 | Food Science and Human Wellness2023，12，2： | 1 |
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