Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery
| Autor: | Tong-Chuan He, Jinyong Luo, Jae Yoon Park, Jan Paul Szatkowski, Pantila Vanichakarn, Li Y, Sun Mh, Andrea T. Deyrup, Anthony G. Montag, Quan Kang, Hongwei Cheng, Rex C. Haydon, Ying Peng, Wei Jiang, Hue H. Luu |
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| Rok vydání: | 2004 |
| Předmět: |
Male
animal structures Bone Morphogenetic Protein 6 Bone Morphogenetic Protein 7 Genetic Vectors GDF2 Bone Morphogenetic Protein 2 Mice Nude Biology Gene delivery Bone morphogenetic protein Injections Intramuscular Viral vector Adenoviridae Cell Line Mice Osteogenesis Transforming Growth Factor beta Genetics medicine Growth Differentiation Factor 2 Animals Bone regeneration Molecular Biology Ossification Reverse Transcriptase Polymerase Chain Reaction Regeneration (biology) Osteoblast Genetic Therapy Cell biology medicine.anatomical_structure embryonic structures Immunology Bone Morphogenetic Proteins Molecular Medicine medicine.symptom Bone Diseases |
| Zdroj: | Gene therapy. 11(17) |
| ISSN: | 0969-7128 |
| Popis: | Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration. |
| Databáze: | OpenAIRE |
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