دورية أكاديمية
The Haploinsufficient Hematopoietic Microenvironment Is Critical to the Pathological Fracture Repair in Murine Models of Neurofibromatosis Type 1.
| العنوان: | The Haploinsufficient Hematopoietic Microenvironment Is Critical to the Pathological Fracture Repair in Murine Models of Neurofibromatosis Type 1. |
|---|---|
| المؤلفون: | Wu, Xiaohua, Chen, Shi, He, Yongzheng, Rhodes, Steven D., Mohammad, Khalid S., Li, Xiaohong, Xianlin Yang, Li Jiang, Nalepa, Grzegorz, Snider, Paige, Robling, Alexander G., Clapp, D. Wade, Conway, Simon J., Guise, Theresa A., Feng-Chun Yang |
| المصدر: | PLoS ONE; 2011, Vol. 6 Issue 9, p1-13, 13p |
| مصطلحات موضوعية: | HAPLOIDY, HEMATOPOIETIC system, SPONTANEOUS fractures, LABORATORY rats, NEUROFIBROMATOSIS, BONE marrow cells, BIOLOGY experiments, SKELETAL dysplasia |
| مستخلص: | Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis). We have developed murine models that phenocopy many of the skeletal dysplasias observed in NF1 patients, including reduced bone mass and fracture non-union. We also show that the development of these skeletal manifestations requires an Nf1 haploinsufficient background in addition to nullizygous loss of Nf1 in mesenchymal stem/ progenitor cells (MSCs) and/or their progenies. This is replicated in two animal models of NF1, PeriCre+;Nf1flox/- and Col2.3Cre+;Nf1flox/-mice. Adoptive transfer experiments demonstrate a critical role of the Nf1+/- marrow microenvironment in the impaired fracture healing in both models and adoptive transfer of WT bone marrow cells improves fracture healing in these mice. To our knowledge, this is the first demonstration of a non-cell autonomous mechanism in non-malignant NF1 manifestations. Collectively, these data provide evidence of a combinatory effect between nullizygous loss of Nf1 in osteoblast progenitors and haploinsufficiency in hematopoietic cells in the development of non-malignant NF1 manifestations. [ABSTRACT FROM AUTHOR] |
| Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| قاعدة البيانات: | Complementary Index |
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