Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis (Small 16/2023)

Zhu, Yinian; Yang, Kunkun; Cheng, Yawen; Liu, Yaoshan; Gu, Ranli; Liu, Xuenan; Líu, Hao; Zhang, Xiao; Liu, Yunsong

doi:10.1002/smll.202370106

Cited by 2 publications

(7 citation statements)

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“…Staurosporine (STS) has been used to induce MSC apoptosis in our previous studies. , To explore optimal induction conditions, we stimulated PLTs with different concentrations of STS and tracked the continuous release of apoVs. These apoVs were separated from apoptotic PLTs (apoPLTs) using an optimized gradient centrifugation scheme (Figure a) .…”

Section: Resultsmentioning

confidence: 99%

“…Taken together, apoVs facilitate osteogenic differentiation of MSCs in vitro and in vivo , filling the gap in PLT-derived apoV functional research. It is noticed that the active concentration of PLT-derived apoVs is half that of the MSC-derived apoVs; 15 directing a small amount of blood could meet treatment needs. Less dosage is also convenient for material loading, broadening the application scenarios of PLT-derived apoVs.…”

Section: Resultsmentioning

confidence: 99%

“…To observe apoV uptake, the red fluorescent cell linker PKH26 (Sigma-Aldrich, USA) was used to label apoVs. , Subsequently, MSCs were incubated with 100 ng/mL labeled apoVs for 0–72 h. The cells were triple rinsed with 0.1 μm-filtered PBS and fixed in 4% PFA for 10 min. Thereafter, the cytoskeleton was labeled with phalloidine at 5 ug/mL, and cellular nuclei were labeled with 6-diamidino-2-phenylindole (DAPI) solution (Zhong Shan-Golden Bridge Biological Technology, China) at 100 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

“…Our group has systemically elucidated detailed characteristics, specific biomarkers, and biological properties of apoVs derived from mesenchymal stem cells (MSCs) . Their functions in bone metabolism have been delineated as promoting osteogenesis and inhibiting osteoclast formation in vitro and in vivo . However, cell culture and expansion are necessary to obtain enough vesicles, which lead to instabilities in both cell and EV function. , A possible immune issue eventuated by a nuclear substance is another concern. − Hence, a promising subpopulation of apoVs that need no cell amplification and without immunogenicity urgently needs to be identified.…”

mentioning

confidence: 99%

“… 14 Their functions in bone metabolism have been delineated as promoting osteogenesis and inhibiting osteoclast formation in vitro and in vivo . 15 However, cell culture and expansion are necessary to obtain enough vesicles, which lead to instabilities in both cell and EV function. 16 , 17 A possible immune issue eventuated by a nuclear substance is another concern.…”

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confidence: 99%

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Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis

Jiang,

Zhu,

Shao

et al. 2023

ACS Nano

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Apoptotic vesicles (apoVs) are apoptotic-cell-derived nanosized vesicles that take on dominant roles in regulating bone homeostasis. We have demonstrated that mesenchymal stem cell (MSC)-derived apoVs are promising therapeutic agents for bone regeneration. However, clinical translation of MSC-derived apoVs has been hindered due to cell expansion and nuclear substance. As another appealing source for apoV therapy, blood cells could potentially eliminate these limitations. However, whether blood cells can release apoVs during apoptosis is uncertain, and the detailed characteristics and biological properties of respective apoVs are not elucidated. In this study, we showed that platelets (PLTs) could rapidly release abundant apoVs during apoptosis in a short time. To recognize the different protein expressions between PLT-derived apoVs and PLTs, we established their precise protein landscape. Furthermore, we identified six proteins specifically enriched in PLT-derived apoVs, which could be considered as specific biomarkers. More importantly, PLT-derived apoVs promoted osteogenesis of MSCs and rescued bone loss via Golgi phosphoprotein 2 (GOLPH2)-induced AKT phosphorylation, therefore, leading to the emergence of their potential in bone regeneration. In summary, we comprehensively determined characteristics of PLT-derived apoVs and confirmed their roles in bone metabolism through previously unrecognized GOPLH2-dependent AKT signaling, providing more understanding for exploring apoV-based therapy in bone tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis

Jiang,

Zhu,

Shao

et al. 2023

ACS Nano

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Apoptotic Extracellular Vesicles Derived from Human Umbilical Vein Endothelial Cells Promote Skin Repair by Enhancing Angiogenesis: From Death to Regeneration

Liu,

Dong,

Pei

2024

IJN

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The promotion of angiogenesis is an effective strategy for skin wound repair. While the transplantation of endothelial cells has shown promise in vascularization, the underlying mechanism remains unclear. Recent studies have suggested that transplanted cells undergo apoptosis in a short period and release apoptotic extracellular vesicles (ApoEVs) that may have therapeutic potential. Methods: In this study, we isolated ApoEVs from human umbilical vein endothelial cells (HUVECs) and characterized their properties. In vitro, we assessed the effects of ApoEVs on the proliferation, migration, and differentiation of endothelial cells and fibroblasts. In vivo, we investigated the therapeutic role of ApoEVs-AT in full-thickness skin wounds, evaluating wound closure rate, re-epithelialization, granulation tissue formation, vascularization, scar area, and collagen 3(Col3)/collagen 1(Col 1) ratio. Results: ApoEVs derived from HUVECs displayed typical characteristics. In vitro, ApoEVs significantly enhanced the proliferation, migration, tube formation, and expression of angiogenic-related genes in endothelial cells and slightly promoted the proliferation and migration of fibroblasts. In vivo, ApoEVs improved the wound closure rate, re-epithelialization, the formation of granulation tissue, and vascularization. Besides, ApoEVs reduced scar formation, accompanied by an increase in the Col 3/ Col 1 ratio. Conclusion: Given their abundant source and effectiveness, this study provided a novel approach for angiogenesis in tissue regeneration and deepened the understanding of from death to regeneration.

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Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis (Small 16/2023)

Cited by 2 publications

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Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis

Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis

Apoptotic Extracellular Vesicles Derived from Human Umbilical Vein Endothelial Cells Promote Skin Repair by Enhancing Angiogenesis: From Death to Regeneration

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