A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indi...A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-βsignaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP-7). This enhancement of BMP-7 in the context of TGF-β in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regulated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-β signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.展开更多
AIM：To evaluate the effect of exogenous recombinant human bone morphogenic protein-7（rhBMP-7）on transforming growth factor-β（TGF-β）-induced epithelial mesenchymal cell transition（EMT）and assessed its antifibr...AIM：To evaluate the effect of exogenous recombinant human bone morphogenic protein-7（rhBMP-7）on transforming growth factor-β（TGF-β）-induced epithelial mesenchymal cell transition（EMT）and assessed its antifibrotic effect via topical application.METHODS：The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells（HECEs）was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid（HA）. EMT markers,fibronectin,E-cadherin,α-smooth muscle actin（α-SMA）,and matrix metaloproteinase-9（MMP-9）,were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7.RESULTS：Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion（31.6%; P〈0.05）,the α-SMA protein level（72.2%; P〈0.01）,and MMP-9 expression（23.6%,P〈0.05）in HECEs compared with cells grown in the presence of TGF-β alone. E-cadherin expression was significantly enhanced（289.7%; P〈0.01）in the presence of rhBMP-7. Topical application of rhBMP-7 combined with 0.1% HA significantly reduced the amount of α-SMA~＋ cells by 43.18%（P〈0.05）at a concentration of 2.5 μg/mL and by 47.73%（P〈0.05）at 25 μg/mL,compared with the control group,without disturbing corneal reepithelization.CONCLUSION：rhBMP-7 attenuates TGF-β-induced EMT in vitro,and topical application of rhBMP-7 reduces keratocyte myodifferentiation during the early wound healing stages in vivo without hindering reepithelization. Topical rhBMP-7 application as biological eye drops seems to be feasible in diseases involving TGF-β-related corneal fibrosis with corneal reepithelization disorders.展开更多
Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15...Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test buplants were coated with 230 μg porcine, high-purified BMP- 3-precipitute per implant. In each case a BMP- 3-couted and an uncoated control-device were implanted into the femoral part of the putellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegrution. Stutistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of tony formed bone of the BMP- 3-coated corundum- blasted or hydroxyapathe- coated Ti- 6Al- 4 V test devices compared to the non-couted controls of the same t）pe （p 〈 0.01, t-test for matched samples）. In both implant groups with BMP-couting a synergetic effect was verifiable although the bone ongrowth in the hydroxyaputite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegrution without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants,as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and im proved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.展开更多
A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured...A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured using standardized methods and left to heal for 3, 7, 14, 21 and 24 d, respectively. The avidin-biotin complex (ABC) method demonstrated an accumulation of positively stained primitive mesenchymal cells at the fracture site in the hematoma stage of bone repair. These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation. Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteoprogenitor cells during fracture healing of the mandible and that BMP may play a significant role in osteogenesis during bone healing.展开更多
Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （...Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.展开更多
Background: Autologous periosteal grafting is used as treatment for articular cartilage defect. Objective: To study the effect of bone morphogenetic protein (BMP) on articular cartilage regeneration following perioste...Background: Autologous periosteal grafting is used as treatment for articular cartilage defect. Objective: To study the effect of bone morphogenetic protein (BMP) on articular cartilage regeneration following periosteal grafting. Methods: 16 healthy 15 week-old New Zealand white rabbits of both sexes (32 knees) were randomly divided into experimental group (group A) and control group (group B). A4.0 mmdiameter full-thickness articular cartilage defect was created in the femoral intercondylar fossa in all rabbits. Following this, a4.0 mmdiameter section of the periosteum was harvested from the anteromedial part of the upper tibial bone. In group A (eight rabbits, 16 knees), the cartilage defect was covered with periosteum, into which 20 μg BMP and 20% Pluronic were injected. In group B (eight rabbits, 16 knees), the cartilage defect was covered with periosteum, into which the same dosage of 0.9% NS (Normal saline) and 20% Pluronic were injected. All rabbits were sacrificed at 4, 8, and 12 weeks postoperatively, the cartilage defect areas were examined macroscopically and microscopically, and the morphology of the chondrocytes and collagen fibers were examined by scanning electron microscopy. Results: The filling of the defects with regenerated tissue was observed in both the group. The most notable improvement was that the cartilage regeneration in group A was obviously superior to that in group B, with the total histological score in group A significantly higher. Conclusion: BMP is an effective factor that could promote regeneration of articular cartilage and lead to successful cartilaginous resurfacing following periosteal展开更多
Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation....Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation. Methods: The BMP2 gene was cloned into a eukaryotic expression vector pcDNA3. Transfected the recombinant into hMSCs by liposome. Immunnohistochemistry and in situ hybridization methods were used to identify the expression of BMP2 mRNA and protein; ALP and Von Kossa stains were performed to identify the BMP2 gene differentiated effect on the hMSCs. Results: The pcDNA3/BMP2 fragments were as large as theory. BMP2 mRNA and protein were expressed and synthesized both in 48 h and 4 weeks after transfection, the ALP and Ca deposit exhibition, which marked the osteogenic lineage of hMSCs, were enhanced and sped. Conclusion: Transfection of pcDNA3/BMP2 is able to provide transient and persistent expression in hMSCs, and promote the MSCs differentiation to osteogenic lineage.展开更多
血管钙化是一个主动可调控的心血管系统异位钙化过程,目前尚无可逆转的有效干预手段。血管钙化和骨形成具有共同的调控机制,骨形态发生蛋白7(bone morphogenetic protein 7,BMP-7)可维持血管平滑肌细胞的收缩表型抑制血管钙化。同时,BM...血管钙化是一个主动可调控的心血管系统异位钙化过程,目前尚无可逆转的有效干预手段。血管钙化和骨形成具有共同的调控机制,骨形态发生蛋白7(bone morphogenetic protein 7,BMP-7)可维持血管平滑肌细胞的收缩表型抑制血管钙化。同时,BMP-7可刺激成骨细胞分化过程,增加骨形成,减少骨吸收降低异位钙化压力。该文系统综述BMP-7影响血管钙化的作用与机制及其目前的临床应用现状。这将有助于以BMP-7为新的分子标志物与潜在药物靶标,研发早期诊断试剂盒及治疗药物,以期实现血管钙化的早期预防与干预,改善患者预后。展开更多
The bone morphogenetic protein(BMP)family of proteins has a multitude of roles throughout the body.It plays important roles in development and in the adult vascular endothelium,by modulating the angiogenic response.Th...The bone morphogenetic protein(BMP)family of proteins has a multitude of roles throughout the body.It plays important roles in development and in the adult vascular endothelium,by modulating the angiogenic response.The endothelial-specific receptor BMP receptor Alk1 is of particular importance in the proper remodeling of the vasculature and its ligand BMP9 has been shown to be a potent inhibitor of neovascularization.Dysregulated BMP signaling has been linked to multiple vascular diseases and can lead to the abnormal angiogenesis.We therefore investigated the role of BMP9/Alk1 signaling in retinal angiogenesis,and its therapeutic implications for vascular pathologies of the eye.展开更多
Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with...Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.展开更多
To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration charact...To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)展开更多
文摘A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-βsignaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP-7). This enhancement of BMP-7 in the context of TGF-β in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regulated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-β signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.
基金Supported by the Soonchunhyang University Research Fund,the WPM project,Ministry of trade,industry&energy(No.10037842)the National Research Foundation of Korea(No.NRF-2016R1C1B2015622)Recombinant human BMP-7 protein was kindly provided by Cellumed Co.,Ltd
文摘AIM：To evaluate the effect of exogenous recombinant human bone morphogenic protein-7（rhBMP-7）on transforming growth factor-β（TGF-β）-induced epithelial mesenchymal cell transition（EMT）and assessed its antifibrotic effect via topical application.METHODS：The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells（HECEs）was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid（HA）. EMT markers,fibronectin,E-cadherin,α-smooth muscle actin（α-SMA）,and matrix metaloproteinase-9（MMP-9）,were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7.RESULTS：Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion（31.6%; P〈0.05）,the α-SMA protein level（72.2%; P〈0.01）,and MMP-9 expression（23.6%,P〈0.05）in HECEs compared with cells grown in the presence of TGF-β alone. E-cadherin expression was significantly enhanced（289.7%; P〈0.01）in the presence of rhBMP-7. Topical application of rhBMP-7 combined with 0.1% HA significantly reduced the amount of α-SMA~＋ cells by 43.18%（P〈0.05）at a concentration of 2.5 μg/mL and by 47.73%（P〈0.05）at 25 μg/mL,compared with the control group,without disturbing corneal reepithelization.CONCLUSION：rhBMP-7 attenuates TGF-β-induced EMT in vitro,and topical application of rhBMP-7 reduces keratocyte myodifferentiation during the early wound healing stages in vivo without hindering reepithelization. Topical rhBMP-7 application as biological eye drops seems to be feasible in diseases involving TGF-β-related corneal fibrosis with corneal reepithelization disorders.
文摘Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test buplants were coated with 230 μg porcine, high-purified BMP- 3-precipitute per implant. In each case a BMP- 3-couted and an uncoated control-device were implanted into the femoral part of the putellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegrution. Stutistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of tony formed bone of the BMP- 3-coated corundum- blasted or hydroxyapathe- coated Ti- 6Al- 4 V test devices compared to the non-couted controls of the same t）pe （p 〈 0.01, t-test for matched samples）. In both implant groups with BMP-couting a synergetic effect was verifiable although the bone ongrowth in the hydroxyaputite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegrution without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants,as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and im proved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.
文摘A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured using standardized methods and left to heal for 3, 7, 14, 21 and 24 d, respectively. The avidin-biotin complex (ABC) method demonstrated an accumulation of positively stained primitive mesenchymal cells at the fracture site in the hematoma stage of bone repair. These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation. Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteoprogenitor cells during fracture healing of the mandible and that BMP may play a significant role in osteogenesis during bone healing.
基金supported by grants from the National Nature Science foundation of China(Grant Nos.30872912 and 30830108)
文摘Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.
文摘Background: Autologous periosteal grafting is used as treatment for articular cartilage defect. Objective: To study the effect of bone morphogenetic protein (BMP) on articular cartilage regeneration following periosteal grafting. Methods: 16 healthy 15 week-old New Zealand white rabbits of both sexes (32 knees) were randomly divided into experimental group (group A) and control group (group B). A4.0 mmdiameter full-thickness articular cartilage defect was created in the femoral intercondylar fossa in all rabbits. Following this, a4.0 mmdiameter section of the periosteum was harvested from the anteromedial part of the upper tibial bone. In group A (eight rabbits, 16 knees), the cartilage defect was covered with periosteum, into which 20 μg BMP and 20% Pluronic were injected. In group B (eight rabbits, 16 knees), the cartilage defect was covered with periosteum, into which the same dosage of 0.9% NS (Normal saline) and 20% Pluronic were injected. All rabbits were sacrificed at 4, 8, and 12 weeks postoperatively, the cartilage defect areas were examined macroscopically and microscopically, and the morphology of the chondrocytes and collagen fibers were examined by scanning electron microscopy. Results: The filling of the defects with regenerated tissue was observed in both the group. The most notable improvement was that the cartilage regeneration in group A was obviously superior to that in group B, with the total histological score in group A significantly higher. Conclusion: BMP is an effective factor that could promote regeneration of articular cartilage and lead to successful cartilaginous resurfacing following periosteal
文摘Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation. Methods: The BMP2 gene was cloned into a eukaryotic expression vector pcDNA3. Transfected the recombinant into hMSCs by liposome. Immunnohistochemistry and in situ hybridization methods were used to identify the expression of BMP2 mRNA and protein; ALP and Von Kossa stains were performed to identify the BMP2 gene differentiated effect on the hMSCs. Results: The pcDNA3/BMP2 fragments were as large as theory. BMP2 mRNA and protein were expressed and synthesized both in 48 h and 4 weeks after transfection, the ALP and Ca deposit exhibition, which marked the osteogenic lineage of hMSCs, were enhanced and sped. Conclusion: Transfection of pcDNA3/BMP2 is able to provide transient and persistent expression in hMSCs, and promote the MSCs differentiation to osteogenic lineage.
文摘血管钙化是一个主动可调控的心血管系统异位钙化过程,目前尚无可逆转的有效干预手段。血管钙化和骨形成具有共同的调控机制,骨形态发生蛋白7(bone morphogenetic protein 7,BMP-7)可维持血管平滑肌细胞的收缩表型抑制血管钙化。同时,BMP-7可刺激成骨细胞分化过程,增加骨形成,减少骨吸收降低异位钙化压力。该文系统综述BMP-7影响血管钙化的作用与机制及其目前的临床应用现状。这将有助于以BMP-7为新的分子标志物与潜在药物靶标,研发早期诊断试剂盒及治疗药物,以期实现血管钙化的早期预防与干预,改善患者预后。
文摘The bone morphogenetic protein(BMP)family of proteins has a multitude of roles throughout the body.It plays important roles in development and in the adult vascular endothelium,by modulating the angiogenic response.The endothelial-specific receptor BMP receptor Alk1 is of particular importance in the proper remodeling of the vasculature and its ligand BMP9 has been shown to be a potent inhibitor of neovascularization.Dysregulated BMP signaling has been linked to multiple vascular diseases and can lead to the abnormal angiogenesis.We therefore investigated the role of BMP9/Alk1 signaling in retinal angiogenesis,and its therapeutic implications for vascular pathologies of the eye.
文摘Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.
文摘To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)
