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Neural Regeneration Research 2010年第21期5卷 1611-1616页

作者： Yan Chang Jingkun Pan Lei Tian Shuilong Guo Yun Luo Xin Cui Yilong Xue Laboratory of Cell Biology Institute of Geriatrics General Hospital of Chinese PLA Beijing 100853 China

In vitro studies have demonstrated that many factors of bone morphogenetic proteins （BMPs） induce cholinergic differentiation of neural stem cells. However, BMP retains the potential to induce increased numbers of cholinergic neurons in central nervous system regions that are rich in cholinergic cells, which is an important determinant of BMP. Therefore, BMP-4 was added to neural stem cell culture medium or the adult rat hippocampal dentate gyrus. Results demonstrated that BMP-4 induced cholinergic differentiation of neural stem cells in vitro and increased the number of cholinergic neurons in the adult rat hippocampal dentate gyrus.

关键词： bone morphogenetic protein neural stem cell induced differentiation cholinergic neuron neural regeneration

Prolonged propagation of rat neural stem cells relies on inhibiting autocrine/paracrine bone morphogenetic protein and platelet derived growth factor signals

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Neural Regeneration Research 2011年第13期6卷 965-971页

作者： Yirui Sun Liangfu Zhou Xing Wu Hua Liu Qiang Yuan Ying Mao Jin Hu Department of Neurosurgery Shanghai Huashan Hospital Fudan University Shanghai 200040 China Shanghai No. 6 People's Hospital Shanghai Jiao Tong University Shanghai 200233 China

Continuous expansion of rat neural stem cell lines has not been achieved due to proliferation arrest and spontaneous differentiation in vitro. In the current study, neural precursor cells derived from the subventricular zone of adult rats spontaneously underwent astroglial and oligodendroglial differentiation after limited propagation. This differentiation was largely induced by autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signals. The results showed that, by inhibiting bone morphogenetic protein and platelet derived growth factor signals, adult rat neural precursor cells could be extensively cultured in vitro as tripotent stem cell lines. In addition to adult rat neural stem cells, we found that bone morphogenetic protein antagonists can promote the proliferation of human neural stem cells. Therefore, the present findings illustrated the role of autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signaling in determining neural stem cell self-renewal and differentiation. By antagonizing both signals, the long-term propagation of rat neural stem cell lines can be achieved.

关键词： neural stem cells cell dormancy proliferation arrest stem cell lines bone morphogenetic protein platelet derived growth factor

Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2

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Chinese Medical Journal 2007年第3期120卷 204-210页

作者： YIN Xiao-xue CHEN Zhong-qiang LIU Zhong-jun MA Qing-jun DANG Geng-ting Department of Orthopaedics Peking University Third HospitalBeijing 100083 China

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.

关键词： Icariine osteoblasts cell proliferation cell differentiation bone morphogenetic protein

Recombinant human bone morphogenetic protein-2 promotes the proliferation of mesenchymal stem cells in vivo and in vitro

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Chinese Medical Journal 2009年第7期122卷 839-843页

作者： LIU Shui-bing HU Pei-zhen HOU Ying LI Peng CAO Wei TIAN Qiong Department of Pharmacology School of Pharmacy FourthMilitary Medical University Xi'an Shaanxi 710032 China Department of Pathology Fourth Military Medical UniversityXi'an S haanxi 710032 China

Background bone morphogenetic protein （BMP） is a member of the superfamily of transforming growth factor-13. Recent studies show that it is an indispensable factor in hematopoiesis. To better characterize the effect of recombinant human BMP （rhBMP）-2 in hematopoiesis, we set out to determine whether rhBMP-2 could promote the proliferation of mesenchymal stem cells （MSCs） and increase the levels of hematopoietic cytokines in MSCs. Methods 2,3-bis （2-methoxy-4-nitro-5-sulfophenyl）-5-（（phenylamino） carbonyl）-2H-tetrazolium hydroxide （XTT）, real-time polymerase chain reaction （PCR） and enzyme-linked immunosorbent assay （ELISA） were used to detect the effects of rhBMP-2 on the proliferation and hematopoietic cytokine levels of MSCs. In addition, MSCs marked with Hoechst33342 were transplanted into BALB/c mice by the intravenous route or intra-bone marrow transplantation, and cluster numbers were counted. Results The XTT test revealed that rhBMP-2 significantly induced proliferation of MSCs in doses ranging from 10 ng/ml to 0.1 mg/ml in a dose-dependent manner. The experiments in vivo showed that there were more clusters of donor cells in bone marrow, spleen, liver and lung of the BMP group than those in the control group after both intra-bone marrow transplantation （P 〈0.001, P 〈0.001, P 〈0.001, and P=0.001, respectively） and intravenous transplantation （P 〈0.001, P 〈0.001, and P 〈0.001 respectively）. The results of real-time PCR and ELISA revealed that rhBMP-2 significantly increased mRNA expressions and protein levels of IL-6, IL-7, IL-11, G-CSF, M-CSF and SCF. Conclusions The treatment with rhBMP-2 promotes the proliferation of MSCs in vivo and in vitro and increases the levels of hematopoietic cytokines in MSCs, which may contribute to the improvement of hematopoietic function.

关键词： bone morphogenetic protein mesenchymal stem cells cell transplantation hematopoietic cytokine

Effect of Danshao Huaxian capsule on Gremlin and bone morphogenetic protein-7 expression in hepatic fibrosis in rats

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World Journal of Gastroenterology 2014年第40期20卷 14875-14883页

作者： Xue-Ke Zhao Ming-Liang Cheng Rong-Min Wu Yu-Mei Yao Mao Mu Juan-Juan Zhu Bao-Fang Zhang Ming-Yu Zhou Department of Infectious Diseases Affiliated Hospital of Guiyang Medical College Department of B Ultrasound Maternal and Child Health Hospital of Guizhou Province

AIM: To observe the effect of Danshao Huaxian capsule (DHC) on the expression of Gremlin and bone morphogenetic protein-7 (BMP-7) in the liver of hepatic fibrosis rats.

关键词： Hepatic fibrosis bone morphogenetic protein Gremlin Transforming growth factor Traditional Chinese herbs

Expression of Vascular Endothelial Growth Factor in bone morphogenetic protein-2 Induced Osteogenesis

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 118-122页

作者：傅德皓 Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

An experimental model of femoral muscular pouch in 20 mice was adopted. The expression of VEGF was examined by in situ hybridization method and immunohistochemical method in bone morphogenetic protein- 2 induced osteogenesis . The experimental results demonstrated that the expression signals of VEGF mRNA and VEGF appeared in cytoplasm during condensation of mesenehymal cell. As the mesenchymal cells differentiated into precartilage, the expression signals decreased in mesenehymal cells, but increased in chondrocytes and kept getting denser in the process of cartilage maturity. The peak expression of VEGF mRNA and VEGF in the experimental group appeared on the 14 th day, accompanied by numerons hypertrophic chondrocytes. When mature cartilage calcified and neu, bone trabecula formed, the expression of VEGF mRNA and VEGF decreased in chondrocytes, but still expressed moderately in the osteoblasts and osteocytes. Signals of VEGF mRNA and VEGF can not be detected in the control groups.

关键词： bone morphogenetic protein vascular endothelial growth factor gene expression in situ hybridization immunohistochemistry

Experimental Study of Porous Beta-tricalcium Phosphate and bone morphogenetic protein/porous Beta-tricalcium Phosphate Complex in Rabbit Mandibular Reconstruction

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 141-143页

作者：李祖兵 School and Hospital of Stomatology Wuhan University Wuhan 430079 China

We investigated the osteogenic characteristic and biodegradation behavior of porous beta-tricalcitum phosphate （ β- TCP ） and bone morphogenetic protein/beta-tricalcium phosphate （ BMP/ β- TCP ） complex in mandibular reconstruction and evaluated the advantages of BMP / β- TCP complex in repairing bone defects. bone defects created in the lower margin of bilateral mandible bodies in 12 rabbits were repaired with β- TCP （ control group ） and BMP/ β- TCP complex （ experimental group ） respectively. The rabbits were euthanized after 2, 4, 8 and 12 weeks and examined by macroscopy, radiography, histology, histomorphometry and image analysis. 2 weeks after surgery, ossftcation of newly-generated tissue in BMP/ β- TCP complex group appeared and after 12 weeks, massive new bone and ossification maturation were seen. However, in β- TCP group without BMP , ossification was not found until 12 weeks after operation. Image analysis showed that bone regeneration rate of BMP/ β- TCP was 30%-40% higher and the degradation rate was 20%- 30% higher than that of β- TCP. Therefore, as a reconstructive material for bone defects, BMP/ β-TCP complex is superior to β-TCP and can be used in oral and maxillofacial surgery.

关键词： porous beta-tricalcium phosphate bone morphogenetic protein reconstruction of bone defects osteoinduction image analysis

The biology of bone morphogenetic protein signaling pathway in cerebrovascular system

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Chinese Neurosurgical Journal 2021年第4期7卷 281-288页

作者： Haishuang Tang Xiaoxi Zhang Gaici Xue Fengfeng Xu Qingsong Wang Pengfei Yang Bo Hong Yi Xu Qinghai Huang Jianmin Liu Qiao Zuo Department of Neurosurgery Changhai HospitalNaval Military Medical University168 Changhai RoadShanghai 200433People’s Republic of China Naval Medical Center of PLA Naval Military Medical UniversityShanghai 200050People’s Republic of China Department of Cardiology the First Medical CentreChinese PLA General HospitalBeijing 100853People’s Republic of China

bone morphogenetic protein belongs to transcription growth factor superfamilyβ;bone morphogenetic protein signal pathway regulates cell proliferation,differentiation,and apoptosis among different *** system supplies sufficient oxygen and blood into brain to maintain its normal *** disorder of cerebrovascular system will result into serious cerebrovascular diseases,which is gradually becoming a major threat to human health in modern *** recent decades,many studies have revealed the underlying biology and mechanism of bone morphogenetic protein signal pathway played in cerebrovascular *** review will discuss the relationship between the two aspects,aiming to provide new perspective for non-invasive treatment and basic research of cerebrovascular diseases.

关键词： bone morphogenetic protein Hemodynamic Neovascularization Cerebrovascular diseases

Extraction, Purification and Identification of bone morphogenetic protein in Conditioned Medium of Osteosarcoma Cell (MG-63)

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The Chinese-German Journal of Clinical Oncology 2003年第4期2卷 234-236,253页

作者：吴华冷燕奎陈安民翟智玲陈继革武汉华中科技大学同济医学院附属同济医院 430030

Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of ***: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ***: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 ***: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).

关键词： osteosarcoma cell conditioned medium bone morphogenetic protein protein purification

BMP(bone morphogenetic protein)

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日本医学介绍 2002年第8期 381-382页

作者：王心赵谨