RIPK1 Coordinates Bone Marrow Mesenchymal Stem Cell Survival by Maintaining Mitochondrial Homeostasis via p53

Qing Tian; Chen Cao; Weijian Qiu; Han Wu; Lijun Zhou; Zhipeng Dai; Zhenwei Li; Songfeng Chen

doi:10.1155/2021/5540149

RIPK1 Coordinates Bone Marrow Mesenchymal Stem Cell Survival by Maintaining Mitochondrial Homeostasis via p53

Stem Cells Int. 2021 Nov 19:2021:5540149. doi: 10.1155/2021/5540149. eCollection 2021.

Authors

Qing Tian¹, Chen Cao², Weijian Qiu¹, Han Wu¹, Lijun Zhou³, Zhipeng Dai², Zhenwei Li¹, Songfeng Chen¹

Affiliations

¹ Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
² Department of Orthopaedics, Henan Provincial People's Hospital, Zhengzhou 450003, China.
³ Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Abstract

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.