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논문 기본 정보

자료유형
학술저널
저자정보
Li Shi-Dan (Army Medical University) Xing Wei (Army Medical University) Wang Shao-Chuan (Army Medical University) Li You-Bin (Army Medical University) Jiang Hao (Affiliated Hospital of Southwest Medical University) Zheng Han-Xuan (Montreal Neurological Hospital) Li Xiao-Ming (Army Medical University) Yang Jing (Army Medical University) Guo De-Bin (Army Medical University) Xie Xiao-Yu (Army Medical University) Jiang Ren-Qing (Third Military Medical University) Fan Chao (Southwest Jiaotong University) Li Lei (Army Medical University) Xu Xiang (Army Medical University) Fei Jun (Army Medical University)
저널정보
대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제55권
발행연도
2023.2
수록면
443 - 456 (14page)
DOI
10.1038/s12276-023-00942-0

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Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

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