The Role of RANKL (TRANCE/TNFSF11), a Tumor Necrosis Factor Family Member, in Skeletal Development: Effects of Gene Knockout and Transgenic Rescue
| العنوان: | The Role of RANKL (TRANCE/TNFSF11), a Tumor Necrosis Factor Family Member, in Skeletal Development: Effects of Gene Knockout and Transgenic Rescue |
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| المؤلفون: | April Mason-Savas, Nacksung Kim, Carole A. MacKay, Sandy C. Marks, Yongwon Choi, Paul R. Odgren |
| المصدر: | Connective Tissue Research. 44:264-271 |
| بيانات النشر: | Informa UK Limited, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | musculoskeletal diseases, Chondrodystrophy, medicine.medical_specialty, Cellular immunity, biology, Transgene, Osteopetrosis, Cell Biology, medicine.disease, Biochemistry, Endocrinology, medicine.anatomical_structure, Rheumatology, Osteoclast, RANKL, Internal medicine, Knockout mouse, medicine, biology.protein, Orthopedics and Sports Medicine, Molecular Biology, Gene knockout |
| الوصف: | We report the skeletal manifestations of restoring RANKL (TNFSF11/TRANCE; see foot note on nomenclature) expression in null mice using a lymphocyte-specific promoter. RANKL was discovered independently by immunologists and bone researchers by virtue of its essential roles in lymph node organogenesis, normal cellular immunity, and osteoclastogenesis. "Rescue" of RANKL knockout mice by a T- and B-cell expressed transgene reversed many immunological manifestations of the knockout, while it had highly selective effects on the skeletal pathology. RANKL-null mice exhibit severe osteopetrosis, no tooth eruption, markedly reduced skeletal growth, and growth plate chondrodystrophy. The transgene induced tartrate-resistant acid phosphatase (TRAP) positive cells in long bones as early as 3 days postpartum, restored marrow spaces in long bones, produced lamellar bone in the diaphyses, and restored osteoclasts at many endosteal sites, but not in periosteum nor the jaws. It did not improve the chondrodystrophy, chondroosseous junction defects, or tooth eruption. The ends of limb and axial skeletal elements remained highly sclerotic while diaphyses became osteopenic, and growth retardation persisted. Together, these results demonstrate the importance of local delivery of RANKL for many skeletal processes. |
| تدمد: | 1607-8438 0300-8207 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::e8d2aa7a579ec8d63e1947ed1d8a5a03 https://doi.org/10.1080/03008200390181753 |
| رقم الأكسشن: | edsair.doi...........e8d2aa7a579ec8d63e1947ed1d8a5a03 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 16078438 03008207 |
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