Tian Qing, Cao Chen, Qiu Weijian, Wu Han, Zhou Lijun, Dai Zhipeng, Li Zhenwei, Chen Songfeng
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Orthopaedics, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Stem Cells Int. 2021 Nov 19;2021:5540149. doi: 10.1155/2021/5540149. eCollection 2021.
Survival of mesenchymal stem cells in the bone marrow is essential for bone marrow microenvironment homeostasis, but the molecular mechanisms remain poorly understood. RIPK1 has emerged as a critical molecule of programmed cell death in tissue homeostasis. However, little is known about the regulation of RIPK1 on bone marrow mesenchymal stem cells (MSCs). Here, we have investigated for the first time the role of RIPK1 in bone marrow MSCs. We have found that RIPK1 knockdown suppressed proliferation, differentiation, and migration in bone marrow MSCs. Furthermore, RIPK1 knockdown resulted in the opening of mitochondrial permeability transition pore (mPTP) and mtDNA damage, leading to mitochondrial dysfunction, and consequently induced apoptosis and necroptosis in bone marrow MSCs. Moreover, we identified that the p53-PUMA axis pathway was involved in mitochondrial dysfunction in RIPK1-deficient bone marrow MSCs. Together, our findings highlighted that RIPK1 was indispensable for bone marrow MSC survival.
间充质干细胞在骨髓中的存活对于骨髓微环境稳态至关重要，但其分子机制仍知之甚少。RIPK1已成为组织稳态中程序性细胞死亡的关键分子。然而，关于RIPK1对骨髓间充质干细胞（MSC）的调控知之甚少。在此，我们首次研究了RIPK1在骨髓间充质干细胞中的作用。我们发现，敲低RIPK1可抑制骨髓间充质干细胞的增殖、分化和迁移。此外，敲低RIPK1导致线粒体通透性转换孔（mPTP）开放和线粒体DNA损伤，进而导致线粒体功能障碍，从而诱导骨髓间充质干细胞凋亡和坏死性凋亡。此外，我们确定p53-PUMA轴通路参与了RIPK1缺陷型骨髓间充质干细胞的线粒体功能障碍。总之，我们的研究结果突出表明，RIPK1对骨髓间充质干细胞的存活不可或缺。
