Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteop...Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. Methods Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells （hMSCs） directionally and were cultured in the presence of vadous concentrations of Icariine. 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase （ALP） and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 （BMP-2） mRNA was detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results Icadine （20 μg/ml） increased significantly the proliferation of human osteoblasts. And, IcarUne （10 μg/ml and 20 μg/ml） increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly （P〈0.05）. BMP-2 mRNA synthesis was elevated significantly in response to Icariine （20 μg/ml）. Conclusions Icadine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.展开更多
Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2...Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.展开更多
破骨细胞是体内唯一负责骨吸收的细胞,成骨细胞是体内负责骨再生的主要细胞,生理情况下,二者保持动态平衡,以维持骨稳态。过去普遍认为,骨代谢的失衡主要受相关炎症因子表达影响,但随着近年来相关研究的逐渐深入,发现自噬与破骨细胞、...破骨细胞是体内唯一负责骨吸收的细胞,成骨细胞是体内负责骨再生的主要细胞,生理情况下,二者保持动态平衡,以维持骨稳态。过去普遍认为,骨代谢的失衡主要受相关炎症因子表达影响,但随着近年来相关研究的逐渐深入,发现自噬与破骨细胞、成骨细胞的分化、凋亡及功能关系密切。腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)是体内能量代谢的重要调节器,同时AMPK参与了调控骨代谢相关细胞的自噬及骨稳态。牙周炎是一种慢性感染性疾病,其典型的症状为牙槽骨吸收。目前在临床上如何更有效地控制牙周炎症水平及牙槽骨的吸收依然是个难题,未来针对AMPK及骨代谢相关细胞自噬水平的检测对于牙周炎的临床防治上具有一定前景。因此,本文就AMPK介导的骨代谢相关细胞自噬调控牙周炎症水平及骨稳态作一综述。展开更多
背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外...背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外分离培养健康成年人骨髓间充质干细胞,培养至第3代时,用含不同浓度尿酸(0,140,280,560μmol/L)的成骨诱导液进行成骨向诱导分化培养,检测细胞成骨分化过程中碱性磷酸酶活性、增殖能力以及Wnt信号通路中Wnt-3α,β-catenin m RNA的表达。结果与结论:各组细胞碱性磷酸酶染色为阳性,尿酸干预后各组细胞碱性磷酸酶活性和增殖能力增高,Wnt信号通路相关基因Wnt-3a、β-catenin的表达上调,且呈现浓度依赖性,各指标在实验组与对照组间比较以及实验组组间比较,差异均有显著性意义(P<0.05)。结果显示尿酸可通过促进Wnt-3a/β-catenin信号通路进而促进骨髓间充质干细胞向成骨细胞增殖和分化,具有浓度依赖性。展开更多
文摘Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. Methods Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells （hMSCs） directionally and were cultured in the presence of vadous concentrations of Icariine. 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase （ALP） and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 （BMP-2） mRNA was detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results Icadine （20 μg/ml） increased significantly the proliferation of human osteoblasts. And, IcarUne （10 μg/ml and 20 μg/ml） increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly （P〈0.05）. BMP-2 mRNA synthesis was elevated significantly in response to Icariine （20 μg/ml）. Conclusions Icadine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.
基金All animal experimental procedures were carried out strictly according to the protocol approved by the University of Hong Kong(HKU)Ethics Committee,Committee on the Use of Live Animals in Teaching and Research(CULATR),(CULATR 5502-20).
文摘Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.
文摘破骨细胞是体内唯一负责骨吸收的细胞,成骨细胞是体内负责骨再生的主要细胞,生理情况下,二者保持动态平衡,以维持骨稳态。过去普遍认为,骨代谢的失衡主要受相关炎症因子表达影响,但随着近年来相关研究的逐渐深入,发现自噬与破骨细胞、成骨细胞的分化、凋亡及功能关系密切。腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)是体内能量代谢的重要调节器,同时AMPK参与了调控骨代谢相关细胞的自噬及骨稳态。牙周炎是一种慢性感染性疾病,其典型的症状为牙槽骨吸收。目前在临床上如何更有效地控制牙周炎症水平及牙槽骨的吸收依然是个难题,未来针对AMPK及骨代谢相关细胞自噬水平的检测对于牙周炎的临床防治上具有一定前景。因此,本文就AMPK介导的骨代谢相关细胞自噬调控牙周炎症水平及骨稳态作一综述。
文摘背景:尿酸作为一种内源性的抗氧化剂,其抗氧化、抗DNA损害作用及发挥促成骨作用近年受到关注。目的:探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路相关基因表达的影响。方法:采用全骨髓贴壁法体外分离培养健康成年人骨髓间充质干细胞,培养至第3代时,用含不同浓度尿酸(0,140,280,560μmol/L)的成骨诱导液进行成骨向诱导分化培养,检测细胞成骨分化过程中碱性磷酸酶活性、增殖能力以及Wnt信号通路中Wnt-3α,β-catenin m RNA的表达。结果与结论:各组细胞碱性磷酸酶染色为阳性,尿酸干预后各组细胞碱性磷酸酶活性和增殖能力增高,Wnt信号通路相关基因Wnt-3a、β-catenin的表达上调,且呈现浓度依赖性,各指标在实验组与对照组间比较以及实验组组间比较,差异均有显著性意义(P<0.05)。结果显示尿酸可通过促进Wnt-3a/β-catenin信号通路进而促进骨髓间充质干细胞向成骨细胞增殖和分化,具有浓度依赖性。
