دورية أكاديمية
CUL4B orchestrates mesenchymal stem cell commitment by epigenetically repressing KLF4 and C/EBPδ
| العنوان: | CUL4B orchestrates mesenchymal stem cell commitment by epigenetically repressing KLF4 and C/EBPδ |
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| المؤلفون: | Ruiqi Yu, Hong Han, Shuxian Chu, Yijun Ding, Shiqi Jin, Yufeng Wang, Wei Jiang, Yuting Liu, Yongxin Zou, Molin Wang, Qiao Liu, Gongping Sun, Baichun Jiang, Yaoqin Gong |
| المصدر: | Bone Research, Vol 11, Iss 1, Pp 1-15 (2023) |
| بيانات النشر: | Nature Publishing Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Physiology |
| مصطلحات موضوعية: | Biology (General), QH301-705.5, Physiology, QP1-981 |
| الوصف: | Abstract Dysregulated lineage commitment of mesenchymal stem cells (MSCs) contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis. The intrinsic cellular mechanism that regulates MSC commitment remains unclear. Here, we identified Cullin 4B (CUL4B) as a critical regulator of MSC commitment. CUL4B is expressed in bone marrow MSCs (BMSCs) and downregulated with aging in mice and humans. Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation. Moreover, depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy. In addition, CUL4B deficiency in MSCs reduced bone strength. Mechanistically, CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδ expression, respectively. The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription. Collectively, this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs, which has therapeutic implications in osteoporosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2095-6231 |
| Relation: | https://doaj.org/toc/2095-6231 |
| DOI: | 10.1038/s41413-023-00263-y |
| URL الوصول: | https://doaj.org/article/45ac476bd6b24c9a890e5c831e5f95e3 |
| رقم الأكسشن: | edsdoj.45ac476bd6b24c9a890e5c831e5f95e3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20956231 |
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| DOI: | 10.1038/s41413-023-00263-y |