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

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.

FADD regulates adipose inflammation, adipogenesis, and adipocyte survival

“…In our study, we observed that protein levels of both RIPK1 and RIPK3 were significantly decreased after Fadd overexpression, while RIPK3 was increased from iWAT of Fadd + /− mice. Moreover, knockdown of Ripk1 inhibits the proliferation of bone marrow mesenchymal stem cells (MSCs) and leads to apoptotic cell death [ 45 ]. Since MSCs share similarities with SVF pre-adipocytes in preserving adipogenic potentials, we speculated that Fadd overexpression may cause a Caspase-3-independent apoptotic cell death in differentiating adipocytes.…”

Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism‐Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu

“…[9,10] Each form of RCD appears to have more or less evidence to support its prevalence in MSCs under pathological stress. [11][12][13] So far, it remains unclear which form of RCD is the culprit for excessive MSC loss when delivered into the injured or diseased liver milieu, and because of this reason, the corresponding interventions are not yet established.…”