دورية أكاديمية
A pathogenic role for brain-derived neurotrophic factor (BDNF) in fibrous dysplasia of bone
| العنوان: | A pathogenic role for brain-derived neurotrophic factor (BDNF) in fibrous dysplasia of bone |
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| المؤلفون: | Palmisano, Biagio, Farinacci, Giorgia, Campolo, Federica, Tavanti, Chiara, Stefano, Alessia, Donsante, Samantha, Ippolito, Ernesto, Giannicola, Giuseppe, Venneri, Mary Anna, Corsi, Alessandro, Riminucci, Mara |
| المساهمون: | Palmisano, Biagio, Farinacci, Giorgia, Campolo, Federica, Tavanti, Chiara, Stefano, Alessia, Donsante, Samantha, Ippolito, Ernesto, Giannicola, Giuseppe, Venneri, Mary Anna, Corsi, Alessandro, Riminucci, Mara |
| بيانات النشر: | Elsevier Ldt New York |
| سنة النشر: | 2024 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | animal model, biopsy, bone fibrosi, bone remodeling, bone resorption, McCune Albright syndrome, osteoclastogenesi, osteogenesi, osteolysis |
| الوصف: | Brain derived neurotrophic factor (BDNF) is a neurotrophin, expressed in the central nervous system and in peripheral tissues, that is regulated by the Gsα/cAMP pathway. In bone, it regulates osteogenesis and stimulates RANKL secretion and osteoclast formation in osteolytic tumors such as Multiple Myeloma. Fibrous dysplasia (FD) of bone is a rare genetic disease of the skeleton caused by gain-of-function mutations of the Gsα gene in which RANKL-dependent enhanced bone resorption is a major cause of bone fragility and clinical morbidity. We observed that BDNF transcripts are expressed in human FD lesions. Specifically, immunolocalization studies performed on biopsies obtained from FD patients revealed the expression of BDNF in osteoblasts and, to a lower extent, in the spindle-shaped cells within the fibrous tissue. Therefore, we hypothesized that BDNF can play a role in the pathogenesis of FD by stimulating RANKL secretion and bone resorption. To test this hypothesis, we used the EF1α-GsαR201C mouse model of the human disease (FD mice). Western blot analysis revealed a higher expression of BDNF in bone segments of FD mice compared to WT mice and the immunolabeling pattern within mouse FD lesions was similar to that observed in human FD. Treatment of FD mice with a monoclonal antibody against BDNF reduced the fibrous tissue along with the number of osteoclasts and osteoblasts within femoral lesions. These results reveal BDNF as a new player in the pathogenesis of FD and a potential molecular mechanism by which osteoclastogenesis may be nourished within FD bone lesions. They also suggest that BDNF inhibition may be a new approach to reduce abnormal bone remodeling in FD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/38331308; volume:181; firstpage:1; lastpage:11; numberofpages:11; journal:BONE; https://hdl.handle.net/11573/1701941Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85184593561 |
| DOI: | 10.1016/j.bone.2024.117047 |
| الإتاحة: | https://doi.org/10.1016/j.bone.2024.117047Test https://hdl.handle.net/11573/1701941Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7B8F5AE0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bone.2024.117047 |
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