Mitochondrial Transfer Regulates Cell Fate Through Metabolic Remodeling in Osteoporosis

Cai, Wenjin; Zhang, Jinglun; Yu, Yiqian; Ni, Yueqi; Wei, Yan; Cheng, Yihong; Han, Litian; Ma, Xinbin; Wei, Hongjiang; Ji, Yaoting; Zhang, Yufeng

doi:10.1002/advs.202204871

Cited by 26 publications

(15 citation statements)

References 54 publications

(86 reference statements)

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“…Moreover, the osteogenesis process depends on energy metabolism, and energy remodeling in macrophages steers the cell fate of osteoblasts. [51] On the one hand, morphology regulation resulted in competition between Arg2 in the arginine hydrolysis pathway and iNOS in the oxidation pathway. On the other hand, the interconversion between ornithine and citrulline maintained a high level of the citrulline product of the arginine oxidation pathway, inhibiting iNOS expression in turn.…”

Section: Discussionmentioning

confidence: 99%

Liver‐Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti‐Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration

et al. 2023

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Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti‐inflammatory reserve (arginase‐2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase‐2 in the anti‐inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti‐inflammatory reserves in bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Liver‐Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti‐Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration

et al. 2023

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“…Under osteoporotic conditions, Cai et al. found that transferring oxidation-damaged mitochondria from M1-like macrophages to MSCs led to circulating succinate accumulation, increasing ROS levels ( 153 ). This activated hypoxia-inducible factor - alpha (HIF-α), promoted IL-1β expression, and affected MSC osteogenic differentiation.…”

Section: Crosstalk Between Mscs and Macrophages During Sepsismentioning

confidence: 99%

Plasticity and crosstalk of mesenchymal stem cells and macrophages in immunomodulation in sepsis

Tao,

Wang,

Liu

et al. 2024

Front. Immunol.

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Sepsis is a multisystem disease characterized by dysregulation of the host immune response to infection. Immune response kinetics play a crucial role in the pathogenesis and progression of sepsis. Macrophages, which are known for their heterogeneity and plasticity, actively participate in the immune response during sepsis. These cells are influenced by the ever-changing immune microenvironment and exhibit two-sided immune regulation. Recently, the immunomodulatory function of mesenchymal stem cells (MSCs) in sepsis has garnered significant attention. The immune microenvironment can profoundly impact MSCs, prompting them to exhibit dual immunomodulatory functions akin to a double-edged sword. This discovery holds great importance for understanding sepsis progression and devising effective treatment strategies. Importantly, there is a close interrelationship between macrophages and MSCs, characterized by the fact that during sepsis, these two cell types interact and cooperate to regulate inflammatory processes. This review summarizes the plasticity of macrophages and MSCs within the immune microenvironment during sepsis, as well as the intricate crosstalk between them. This remains an important concern for the future use of these cells for immunomodulatory treatments in the clinic.

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“…Interestingly, MitoEVs can contain both healthy or damaged mitochondria, with different physiopathological consequences on target cells. Recent research has provided solid evidence to support that mitochondria are released from cells for transcellular degradation or transferred to other cells as metabolic support or regulatory messengers [ 36 , 37 , 38 , 39 ].…”

Section: Mitoevsmentioning

confidence: 99%

The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools

Sanz-Ros

Mas-Bargues

Romero-García

et al. 2023

IJMS

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The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria and can lead to the release of mitochondrial constituents to the extracellular milieu through mitochondrial extracellular vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, and protein complexes of the respiratory chain, and the largest MitoEVs can even transport whole mitochondria. Macrophages ultimately engulf these MitoEVs to undergo outsourced mitophagy. Recently, it has been reported that MitoEVs can also contain healthy mitochondria, whose function seems to be the rescue of stressed cells by restoring the loss of mitochondrial function. This mitochondrial transfer has opened the field of their use as potential disease biomarkers and therapeutic tools. This review describes this new EVs-mediated transfer of the mitochondria and the current application of MitoEVs in the clinical environment.

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Mitochondrial Transfer Regulates Cell Fate Through Metabolic Remodeling in Osteoporosis

Cited by 26 publications

References 54 publications

Liver‐Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti‐Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration

Liver‐Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti‐Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration

Plasticity and crosstalk of mesenchymal stem cells and macrophages in immunomodulation in sepsis

The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools

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