Thymidine Kinase-Mediated Shut Down of Bone Morphogenetic Protein-4 Expression Allows Regulated Bone Production (873 views)
Current Gene Therapy (ISSN: 1566-5232, 1875-5631), 2013 Jun 1; 13(3): 202-210.
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Paper type: Journal Article,
Impact factor: 4.906, 5-year impact factor: 4.087
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84878661287&partnerID=40&md5=d34b8cfd0d6edde8d279198bb905138e
Keywords: Bone Production Regulation, Fg-B4, Adenovirus Vector, Bone Morphogenetic Protein 4, Ganciclovir, Thymidine Kinase, Animal Experiment, Animal Tissue, Apoptosis, Article, Bone Densitometry, Cell Death, Cell Differentiation, Cell Infiltration, Controlled Study, Dual Energy X Ray Absorptiometry, Exostosis, Fibrosis, Histology, Human, Human Cell, Inflammation, Micro-Computed Tomography, Mouse, Nick End Labeling, Nonhuman, Ossification, Protein Expression, Upregulation, Bone And Bones, Bone Development, Gene Expression Regulation, Gene Transfer Techniques, Genetic Vectors, Nude, Osteogenesis, Quadriceps Muscle, Simplexvirus, Transgenes, Mus Musculus, Oryctolagus Cuniculus,
Affiliations:
*** IBB - CNR ***
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy
CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy
Dipartimento di Scienze Biomorfologiche e Funzionali, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy
References:
Not available.
Current Gene Therapy (ISSN: 1566-5232, 1875-5631), 2013 Jun 1; 13(3): 202-210.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.906, 5-year impact factor: 4.087
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84878661287&partnerID=40&md5=d34b8cfd0d6edde8d279198bb905138e
Keywords: Bone Production Regulation, Fg-B4, Adenovirus Vector, Bone Morphogenetic Protein 4, Ganciclovir, Thymidine Kinase, Animal Experiment, Animal Tissue, Apoptosis, Article, Bone Densitometry, Cell Death, Cell Differentiation, Cell Infiltration, Controlled Study, Dual Energy X Ray Absorptiometry, Exostosis, Fibrosis, Histology, Human, Human Cell, Inflammation, Micro-Computed Tomography, Mouse, Nick End Labeling, Nonhuman, Ossification, Protein Expression, Upregulation, Bone And Bones, Bone Development, Gene Expression Regulation, Gene Transfer Techniques, Genetic Vectors, Nude, Osteogenesis, Quadriceps Muscle, Simplexvirus, Transgenes, Mus Musculus, Oryctolagus Cuniculus,
Affiliations:
*** IBB - CNR ***
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy
CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy
Dipartimento di Scienze Biomorfologiche e Funzionali, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy
References:
Not available.
Thymidine Kinase-Mediated Shut Down of Bone Morphogenetic Protein-4 Expression Allows Regulated Bone Production
Bone morphogenetic Proteins (BMPs) are growth factors also involved in ossification and chondrogenesis that have generated interest for their efficiency in inducing bone neo-synthesis. BMPs expression in engineered cells has been successful in stimulating osteoblastic differentiation and ectopic and orthotopic bone formation in vivo. We have previously shown that an adenoviral vector expressing bone morphogenetic protein type-4 (BMP-4) is able to efficiently drive bone formation in a rabbit model of discontinuous bone lesions. However, unregulated secretion of BMPs has also been implicated in bone overproduction and exostosis. We have constructed a replication-defective first generation adenoviral (FG-Ad) vector containing a cassette for the expression of BMP-4 associated with the Herpes Simplex virus thymidine kinase (TK) gene (FG-B4TK) in order to shut down BMP-4 expression and, therefore, regulate bone production. TK expression does not interfere with BMP-4 ability to induce ectopic bone formation in athymic nude mice. Administration of ganciclovir blocks ectopic bone production in quadriceps muscle transduced with the FG-B4TK with no effect on the contralateral muscle transduced with a vector expressing only BMP-4. Histological findings confirmed the pro-apoptotic activity of TK and the reduction of mineralized areas in the quadriceps transduced with FG-B4TK in mice treated with ganciclovir. We have generated a system to block BMP-4 secretion by inducing apoptosis in transduced cells therefore blocking unwanted bone formation. This system is an additional tool to generate regulated amount of bone in discontinuous bone lesions and can be easily coupled with biomaterials capable of recruiting cells and generating a local bioreactor.
Bone morphogenetic Proteins (BMPs) are growth factors also involved in ossification and chondrogenesis that have generated interest for their efficiency in inducing bone neo-synthesis. BMPs expression in engineered cells has been successful in stimulating osteoblastic differentiation and ectopic and orthotopic bone formation in vivo. We have previously shown that an adenoviral vector expressing bone morphogenetic protein type-4 (BMP-4) is able to efficiently drive bone formation in a rabbit model of discontinuous bone lesions. However, unregulated secretion of BMPs has also been implicated in bone overproduction and exostosis. We have constructed a replication-defective first generation adenoviral (FG-Ad) vector containing a cassette for the expression of BMP-4 associated with the Herpes Simplex virus thymidine kinase (TK) gene (FG-B4TK) in order to shut down BMP-4 expression and, therefore, regulate bone production. TK expression does not interfere with BMP-4 ability to induce ectopic bone formation in athymic nude mice. Administration of ganciclovir blocks ectopic bone production in quadriceps muscle transduced with the FG-B4TK with no effect on the contralateral muscle transduced with a vector expressing only BMP-4. Histological findings confirmed the pro-apoptotic activity of TK and the reduction of mineralized areas in the quadriceps transduced with FG-B4TK in mice treated with ganciclovir. We have generated a system to block BMP-4 secretion by inducing apoptosis in transduced cells therefore blocking unwanted bone formation. This system is an additional tool to generate regulated amount of bone in discontinuous bone lesions and can be easily coupled with biomaterials capable of recruiting cells and generating a local bioreactor.
Thymidine Kinase-Mediated Shut Down of Bone Morphogenetic Protein-4 Expression Allows Regulated Bone Production
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Thymidine Kinase-Mediated Shut Down of Bone Morphogenetic Protein-4 Expression Allows Regulated Bone Production
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12 Records (10 excluding Abstracts).
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Total 5 year impact factor: 55.854 (45.671 excluding Abstracts).
Total impact factor: 64.108 (53.518 excluding Abstracts).
Total 5 year impact factor: 55.854 (45.671 excluding Abstracts).
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