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1.
J Surg Res ; 180(2): e73-81, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22560858

RESUMO

PURPOSE: We administered recombinant interleukin (IL)-4 and recombinant IL-13 locally into the air pouch of mice to improve bone resorption induced by ultra-high-molecular-weight polyethylene (UHMWPE) particles. METHODS: Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor. We stimulated the bone-implanted pouches with the UHMWPE suspension. We divided UHMWPE-containing mice into four study groups to receive injections of phosphate-buffered saline (control), IL-4 alone, IL-13 alone, or IL-4 and IL-13 into the pouches. We harvested the tissues at 14 d after treatment for molecular and histological analyses. RESULTS: The inhibitory effect of IL-4 was stronger than that of IL-13 toward osteoclast differentiation and osteoblast for the induction of osteoprotegerin production and down-regulation of receptor for activation of nuclear factor-κB ligand production. Furthermore, the combined treatment with both IL-4 and 1L-13 had a more important role in inhibiting bone resorption in these pouches with UHMWPE stimulation, compared with IL-4 or IL-13 treatment alone. CONCLUSIONS: Local administration of recombinant IL-4 and IL-13 may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.


Assuntos
Interleucina-13/uso terapêutico , Interleucina-4/uso terapêutico , Osteólise/tratamento farmacológico , Polietilenos/toxicidade , Fosfatase Ácida/análise , Animais , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Isoenzimas/análise , Camundongos , Camundongos Endogâmicos BALB C , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/análise , Proteínas Recombinantes/uso terapêutico , Fosfatase Ácida Resistente a Tartarato
2.
Connect Tissue Res ; 53(6): 528-34, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22827452

RESUMO

OBJECTIVE: Adenovirus expressing small interfering RNA (siRNA)-targeting BMPR-IB was locally administered into the air pouch of mice to improve bone resorption induced by ultra-high molecular weight polyethylene (UHMWPE) particles. METHOD: Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor. The bone-implanted pouches were stimulated with the UHMWPE suspension. UHMWPE-containing mice were divided into three study groups to receive injections of adenovirus expressing BMPR-IB siRNA (BMPR-IB group), adenovirus expressing missense siRNA, and virus-free culture medium (control group) into the pouches, respectively. The tissues were harvested at 14 days after the treatment for molecular and histological analyses. RESULTS: Adenovirus-mediated BMPR-IB siRNA treatment significantly improved UHMWPE particle-induced bone resorption, reduced TRAP and RANK gene and protein expression levels, and diminished the number of TRAP-positive cells. Furthermore, the BMPR-IB siRNA inhibited osteoclast differentiation by targeting osteoblast for the induction of osteoprotegerin formation and downregulation of receptor for activation of nuclear factor-κB ligand production. CONCLUSIONS: This study suggested that loss of bone morphogenetic protein signaling by BMPR-IB siRNA directs osteoblasts to decrease bone destruction in part by downregulating osteoclastogenesis through the receptor for activation of nuclear factor-κB ligand-osteoprotegerin pathway. Local administration of adenovirus expressing siRNA-targeting BMPR-IB may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.


Assuntos
Adenoviridae , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/biossíntese , Reabsorção Óssea/metabolismo , Vetores Genéticos , Polietileno/efeitos adversos , RNA Interferente Pequeno , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Transplante Ósseo , Modelos Animais de Doenças , Inativação Gênica , Camundongos , Camundongos Endogâmicos BALB C , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Polietileno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transplante Isogênico
3.
Nat Commun ; 12(1): 4534, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312395

RESUMO

Benzene is a widely used commodity chemical, which is currently produced from fossil resources. Lignin, a waste from lignocellulosic biomass industry, is the most abundant renewable source of benzene ring in nature. Efficient production of benzene from lignin, which requires total transformation of Csp2-Csp3/Csp2-O into C-H bonds without side hydrogenation, is of great importance, but has not been realized. Here, we report that high-silica HY zeolite supported RuW alloy catalyst enables in situ refining of lignin, exclusively to benzene via coupling Bronsted acid catalyzed transformation of the Csp2-Csp3 bonds on the local structure of lignin molecule and RuW catalyzed hydrogenolysis of the Csp2-O bonds using the locally abstracted hydrogen from lignin molecule, affording a benzene yield of 18.8% on lignin weight basis in water system. The reaction mechanism is elucidated in detail by combination of control experiments and density functional theory calculations. The high-performance protocol can be readily scaled up to produce 8.5 g of benzene product from 50.0 g lignin without any saturation byproducts. This work opens the way to produce benzene using lignin as the feedstock efficiently.


Assuntos
Benzeno/química , Hidrogênio/química , Lignina/química , Água/química , Zeolitas/química , Benzeno/síntese química , Catálise , Ligação de Hidrogênio , Nanopartículas Metálicas/química , Metais/química , Modelos Químicos , Estrutura Molecular , Oxirredução
4.
PLoS One ; 9(3): e92908, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24658746

RESUMO

Mesenchymal stem cells (MSCs) are multipotent progenitors, which can undergo self-renewal and give rise to multi-lineages. A great deal of attentions have been paid to their potential use in regenerative medicine as potential therapeutic genes can be introduced into MSCs. Genetic manipulations in MSCs requires effective gene deliveries. Recombinant adenoviruses are widely used gene transfer vectors. We have found that although MSCs can be infected in vitro by adenoviruses, high virus titers are needed to achieve high efficiency. Here, we investigate if the commonly-used cationic polymer Polybrene can potentiate adenovirus-mediated transgene delivery into MSCs, such as C2C12 cells and iMEFs. Using the AdRFP adenovirus, we find that AdRFP transduction efficiency is significantly increased by Polybrene in a dose-dependent fashion peaking at 8 µg/ml in C2C12 and iMEFs cells. Quantitative luciferase assay reveals that Polybrene significantly enhances AdFLuc-mediated luciferase activity in C2C12 and iMEFs at as low as 4 µg/ml and 2 µg/ml, respectively. FACS analysis indicates that Polybrene (at 4 µg/ml) increases the percentage of RFP-positive cells by approximately 430 folds in AdRFP-transduced iMEFs, suggesting Polybrene may increase adenovirus infection efficiency. Furthermore, Polybrene can enhance AdBMP9-induced osteogenic differentiation of MSCs as early osteogenic marker alkaline phosphatase activity can be increased more than 73 folds by Polybrene (4 µg/ml) in AdBMP9-transduced iMEFs. No cytotoxicity was observed in C2C12 and iMEFs at Polybrene up to 40 µg/ml, which is about 10-fold higher than the effective concentration required to enhance adenovirus transduction in MSCs. Taken together, our results demonstrate that Polybrene should be routinely used as a safe, effective and inexpensive augmenting agent for adenovirus-mediated gene transfer in MSCs, as well as other types of mammalian cells.


Assuntos
Adenoviridae/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Brometo de Hexadimetrina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Transdução Genética , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Citometria de Fluxo , Expressão Gênica , Genes Reporter , Humanos , Camundongos , Transgenes
5.
Stem Cells Dev ; 23(12): 1405-16, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24517722

RESUMO

Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing bone formation. Here, we investigate whether BMP9 can effectively induce odontogenic differentiation of the stem cells from mouse apical papilla (SCAPs). Using a reversible immortalization system expressing SV40 T flanked with Cre/loxP sites, we demonstrate that the SCAPs can be immortalized, resulting in immortalized SCAPs (iSCAPs) that express mesenchymal stem cell markers. BMP9 upregulates Runx2, Sox9, and PPARγ2 and odontoblastic markers, and induces alkaline phosphatase activity and matrix mineralization in the iSCAPs. Cre-mediated removal of SV40 T antigen decreases iSCAP proliferation. The in vivo stem cell implantation studies indicate that iSCAPs can differentiate into bone, cartilage, and, to lesser extent, adipocytes upon BMP9 stimulation. Our results demonstrate that the conditionally iSCAPs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages, including osteo/odontoblastic differentiation. Thus, the reversibly iSCAPs may serve as an important tool to study SCAP biology and SCAP translational use in tooth engineering. Further, BMP9 may be explored as a novel and efficacious factor for odontogenic regeneration.


Assuntos
Diferenciação Celular/genética , Papila Dentária/crescimento & desenvolvimento , Fator 2 de Diferenciação de Crescimento/genética , Odontogênese , Animais , Proliferação de Células/genética , Papila Dentária/citologia , Regulação da Expressão Gênica no Desenvolvimento , Fator 2 de Diferenciação de Crescimento/biossíntese , Camundongos , Odontoblastos/metabolismo , Regeneração , Células-Tronco/metabolismo
6.
Biomaterials ; 34(1): 150-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23079666

RESUMO

Aseptic loosening (AL) is the single most common complication of total joint arthroplasty. The critical factor may contribute to loosening is the adverse tissue response to wear debris. A growing body of literature suggests that BMPs influence the formation and activity of osteoclasts, and BMP signaling plays an important role in the osteoclast formation. In this study, we have employed an RNA interference approach by transfecting a small interfering RNA (siRNA) specific for BMPR-II, to determine the possible importance of this receptor as a target for UHMWPE (Ultra high molecular weight polyethylene) induced osteoclastogenesis in the air pouch model in vivo. Meanwhile, in order to further elucidation of the mechanism of BMPR-II signaling pathway in osteoclast formation, we investigated the effects of siBMPR-II toward RANKL induced osteoclast differentiation in vitro. The present study showed that locally injection of adenovirus-mediated siRNA targeting BMPR-II appears to be a feasible and effective candidate to treat or prevent wear debris-associated osteolysis. Furthermore, we revealed that the effects of BMPR-II signaling on osteoclast formation are mediated directly by osteoclast itself, as well as indirectly by altered expression of RANKL and OPG in osteoblast.


Assuntos
Adenoviridae/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Polietilenos/farmacologia , RNA Interferente Pequeno/metabolismo , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Adenoviridae/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Diferenciação Celular/efeitos dos fármacos , Feminino , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Interferência de RNA/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Coloração e Rotulagem , Fosfatase Ácida Resistente a Tartarato
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(10): 1709-13, 2011 Oct.
Artigo em Zh | MEDLINE | ID: mdl-22027773

RESUMO

OBJECTIVE: To test the effect of recombinant interleukin-4 (IL-4) and recombinant osteoprotegerin (OPG) in suppressing bone resorption induced by polyethylene wear particles.. METHODS: A cranial bone allograft was introduced into the air pouches induced on the back of BALB/c mice, followed by injection of 1 ml suspension of polyethylene particles into the pouches. The mouse models were then divided into 3 groups to receive injections of saline (control), IL-4 alone, or IL-4 and OPG into the pouches. The tissues were harvested 21 days after bone implantation for molecular and histological analyses. RESULTS: Polyethylene wear particles-stimulated inflammatory responses (increased cellular infiltration and IL-1 and TNF production) were markedly reduced by IL-4 treatment either alone or combined with OPG (P<0.05). Polyethylene particles significantly increased tartrate-resistant acid phosphatase (TRAP) staining and bone absorption of the implanted bone graft, and IL-4 treatment, either alone or combined with OPG, obviously reduced the osteolysis induced by polyethylene particles (P<0.05). CONCLUSION: IL-4 offers protection against polyethylene wear debris-induced inflammation and bone resorption in this mouse model. IL-4 combined with OPG can be a feasible and effective therapeutic approach to the treatment and prevention of polyethylene wear debris-associated osteolysis and aseptic loosening of the prosthetic components.


Assuntos
Interleucina-4/farmacologia , Dispositivos de Fixação Ortopédica/efeitos adversos , Osteólise/prevenção & controle , Osteoprotegerina/farmacologia , Polietileno/antagonistas & inibidores , Animais , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/prevenção & controle , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Osteólise/induzido quimicamente , Proteínas Recombinantes/farmacologia
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