دورية أكاديمية
A genetic mouse model mimicking MET related human osteofibrous dysplasia is characterized by delays in fracture repair and defective osteogenesis.
| العنوان: | A genetic mouse model mimicking MET related human osteofibrous dysplasia is characterized by delays in fracture repair and defective osteogenesis. |
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| المؤلفون: | Hong G; Traumatology & Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.; Department of Orthopedic, the Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.; Division of Orthopaedic Surgery, University of Alberta, Edmonton, Alberta, Canada., Xie W; Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Ahmed K; Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Oborn C; Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada., Soltys CL; Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada., Kannu P; Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jul 31; Vol. 38 (14), pp. e23810. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Osteogenesis*/genetics , Proto-Oncogene Proteins c-met*/genetics , Proto-Oncogene Proteins c-met*/metabolism , Fracture Healing*/genetics , Bone Diseases, Developmental*/genetics , Bone Diseases, Developmental*/pathology , Disease Models, Animal* , Fibrous Dysplasia of Bone*/genetics , Fibrous Dysplasia of Bone*/pathology , Fibrous Dysplasia of Bone*/metabolism, Animals ; Mice ; Humans ; Osteoblasts/metabolism ; Osteoblasts/pathology ; Mutation ; Cell Differentiation ; Mice, Inbred C57BL ; Male |
| مستخلص: | Osteofibrous dysplasia (OFD) is a rare, benign, fibro-osseous lesion that occurs most commonly in the tibia of children. Tibial involvement leads to bowing and predisposes to the development of a fracture which exhibit significantly delayed healing processes, leading to prolonged morbidity. We previously identified gain-of-function mutations in the MET gene as a cause for OFD. In our present study, we test the hypothesis that gain-of-function MET mutations impair bone repair due to reduced osteoblast differentiation. A heterozygous Met exon 15 skipping (Met Δ15 -HET) mouse was created to imitate the human OFD mutation. The mutation results in aberrant and dysregulation of MET-related signaling determined by RNA-seq in the murine osteoblasts extracted from the wide-type and genetic mice. Although no gross skeletal defects were identified in the mice, fracture repair was delayed in Met Δ15 -HET mice, with decreased bone formation observed 2-week postfracture. Our data are consistent with a novel role for MET-mediated signaling regulating osteogenesis. (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.) |
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| معلومات مُعتمدة: | 166064 CIHR; WCHRI |
| فهرسة مساهمة: | Keywords: Met; RNA‐seq; fracture; osteofibrous dysplasia; osteogenesis |
| المشرفين على المادة: | EC 2.7.10.1 (Proto-Oncogene Proteins c-met) |
| SCR Disease Name: | Osteofibrous Dysplasia |
| تواريخ الأحداث: | Date Created: 20240723 Date Completed: 20240723 Latest Revision: 20240723 |
| رمز التحديث: | 20240725 |
| DOI: | 10.1096/fj.202400075RR |
| PMID: | 39042586 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.202400075RR |