Effect of Anti‐TGF‐β Treatment in a Mouse Model of Severe Osteogenesis Imperfecta
| Autor: | Sami Abdullah, Josephine T. Tauer, Frank Rauch |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Bone tissue Bone and Bones Mice 03 medical and health sciences 0302 clinical medicine Osteogenesis Transforming Growth Factor beta Internal medicine medicine Animals Orthopedics and Sports Medicine Neutralizing antibody Mice Knockout Extracellular Matrix Proteins biology Chemistry Acid phosphatase Transforming growth factor beta Osteogenesis Imperfecta medicine.disease Antibodies Neutralizing Resorption Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Osteogenesis imperfecta biology.protein Alkaline phosphatase Molecular Chaperones Transforming growth factor |
| Zdroj: | Journal of Bone and Mineral Research. 34:207-214 |
| ISSN: | 1523-4681 0884-0431 |
| Popis: | Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap-/- mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF-β) neutralizing antibody 1D11 rescues the bone phenotype. In the present study, we investigated TGF-β signaling in a mouse model of severe dominant OI with a high incidence of spontaneous fractures, Col1a1Jrt/+ mice, and the effect of TGF-β neutralizing antibody 1D11 on bone phenotype in 8-week-old mice. Col1a1Jrt/+ mice had elevated TGF-β signaling in bone tissue. Treatment of Col1a1Jrt/+ mice with 1D11 was associated with increased bone length but had no significant effect on bone mass or bone mechanical properties, and no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity) or resorption (tartrate-resistant acid phosphatase) were found. Our data thus indicate that the TGF-β neutralizing antibody 1D11 is not effective in a mouse model of dominant OI with a high incidence of spontaneous fractures. © 2018 American Society for Bone and Mineral Research. |
| Databáze: | OpenAIRE |
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