Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat. Li, JZ; Li, H; Sasaki, T; Holman, D; Beres, B; Dumont, RJ; Pittman, DD; Hankins, GR; Helm, GA Gene therapy
10
1735-43
2003
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Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 x 10(5) PFU/well of BMP viral vector was 4890 x 10(-12) U/well for ADCMVBMP-9, 302 x 10(-12) U/well for ADCMVBMP-4, 220 x 10(-12) U/well for ADCMVBMP-6, 45 x 10(-12) U/well for ADCMVBMP-2, and 0.43 x 10(-12) U/well for ADCMVBMP-7. The average volume of new bone induced by 10(7) PFU of BMP vector in athymic nude rats was 0.37+/-0.03 cm(3) for ADCMVBMP-2, 0.89+/-0.07 cm(3) for ADCMVBMP-4, 1.02+/-0.07 cm(3) for ADCMVBMP-6, 0.24+/-0.05 cm(3) for ADCMVBMP-7, and 0.63+/-0.07 cm(3) for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10(8) PFU induced 0.10+/-0.03 cm(3) of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10(7) PFU induced more bone, with an average volume of 0.29+/-0.01 cm(3). | 12939640
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Immunolocalization of vgr (BMP-6, DVR-6), a TGF-beta related cytokine, to Schwann cells of the rat peripheral nervous system: expression patterns are not modulated by autoimmune disease. Schluesener, H J, et al. Glia, 13: 75-8 (1995)
1995
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The transforming growth factors type beta (TGF-beta) have been implicated in regulation of peripheral nervous system inflammation and regeneration. Here we demonstrate expression of a TGF-beta-related bone morphogenetic protein, the vgr (BMP-6, DVR-6) in Schwann cells of the rat peripheral nervous system. The expression of vgr in the peripheral nervous system suggests that this factor and probably other TGF-beta-related bone morphogenetic proteins might participate in Schwann cell function during aspects of peripheral nervous system physiology and pathology. However, we did not observe changes in expression patterns in response to autoimmune inflammation (experimental autoimmune neuritis) of the peripheral nervous system. | 7751058
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Expression of BMP-6, a TGF-beta related morphogenetic cytokine, in rat radial glial cells. Schluesener, H J and Meyermann, R Glia, 12: 161-4 (1994)
1994
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Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily of cytokines. The bone morphogenetic proteins and homologous cytokines participate in realization of the genetic body plan by regulating homeotic gene expression, embryonic development, and neurogenesis. Here we demonstrate expression of BMP-6 in rat radial glial cells which are involved in embryonic organisation of the central nervous system. Thus, morphogenetic cytokines like BMP-6 might contribute to radial glial cell function in organizing the migration of immature neurons during the development of the CNS cortex. | 7868189
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