Osteoclast-derived apoptotic bodies show extended biological effects of parental cell in promoting bone defect healing

Ma, Qinyu; Liang, Mengmeng; Limjunyawong, Nathachit; Yang, Dan; Xing, Junchao; Li, Jianmei; Xu, Jiake; Dou, Ce

doi:10.7150/thno.45170

Cited by 44 publications

(48 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We obtained primary MSCs and BMMs from bone marrow of 11-week-old C57BL/6 mice as previously described 47 , 48 . After mice were sacrificed, the femurs and tibias were harvested under aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

“…To isolate MSCs, we cultured BMCs in alpha minimal essential medium (α-MEM; HyClone, USA) for 24 h and then removed the nonadherent cells to obtain MSCs. In addition, we isolated EPCs from mouse peripheral blood as previously described 48 . Cells were maintained in α-MEM supplemented with 10% FBS (BioInd, Israel) and 100 U·mL −1 penicillin/streptomycin (Solarbio, Beijing, China) in a 37 °C incubator with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…For further analysis, FC values were normalized using log2 ratios. Data visualization, including hierarchical clustering, Venn diagram analysis and volcano plots, was performed as previously described 48 . We generated PCA plots using the ggfortify R package.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were then incubated with 500 μL of AB medium or with complete medium as the vehicle. After 6 h, endothelial cells linked by tubes were observed and quantified as previously described 48 .…”

Section: Methodsmentioning

confidence: 99%

“…DBM was detached from limb bones of cattle and treated as previously described 48 and was divided into 2.5 mm × 2.5 mm blocks. The blocks were soaked with 75% ethanol for 3 h and rinsed with PBS.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling

Liang

et al. 2021

Bone Res

Self Cite

View full text Add to dashboard Cite

Bone remodeling is precisely coordinated by bone resorption and formation. Apoptotic osteoclasts generate large amounts of apoptotic bodies (ABs) marking the end of the bone resorption phase, whereas the functions of osteoclast-derived ABs remain largely unknown. Here, we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions. ABs were isolated from apoptotic bone marrow macrophages, preosteoclasts, and mature osteoclasts induced by staurosporine. Proteomic signature analysis with liquid chromatography-tandem mass spectrometry suggested marked protein cargo differences among the different ABs. Further bioinformatic analysis showed that the proteomic signatures of the ABs were highly similar to those of their parental cells. Functionally, pOC-ABs induced endothelial progenitor cell differentiation and increased CD31hiEmcnhi endothelial cell formation in a murine bone defect model via their PDGF-BB cargo. mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling. In summary, we mapped the detailed proteomic landscapes of ABs derived from osteoclasts and showed that their potential biological roles are important in coupling bone formation with resorption during bone remodeling.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling

Liang

et al. 2021

Bone Res

Self Cite

View full text Add to dashboard Cite

show abstract

Phospholipid‐Modified Titanium Surface‐Loaded Apoptotic Extracellular Vesicles Promote Early Angiogenesis and Improve Implant Osseointegration Through Immune Regulation

Chen,

Ning,

Zhu

et al. 2024

Adv Materials Inter

View full text Add to dashboard Cite

Tissue‐engineered extraction products, such as apoptotic extracellular vesicles (ApoEVs), significantly promote tissue regeneration, endowing them with the potential to improve osseointegration. However, there is an urgent need to determine how to effectively load these materials onto a material surface to maximize their function. Considering that all such products have a phospholipid bilayer, a phospholipid‐modified implant coating is designed that can effectively load tissue‐engineered products with a phospholipid bilayer structure. ApoEVs are effectively loaded onto the surface and the osteogenic effect improved, achieving good osseointegration. In vitro experiments show that this material improves angiogenesis by promoting macrophage M1 polarization and NO secretion in the early stages. In vivo experiments show that after implantation, it effectively improve the peri‐implant vascularization of the implant, thereby improving the new bone formation ability and osseointegration. This study provides a universal solution for loading vesicular tissue‐engineered products onto an implant surface and validates its ability to improve bone fusion using ApoEVs as an example while exploring its mechanism.

show abstract

Apoptotic Bodies Derived from Fibroblast‐Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR‐339‐5p/KEAP1/Nrf2 Axis

Yu,

Chen,

Yang

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast‐like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1‐to‐M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1‐Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR‐339‐5p to exert therapeutic effects. In conclusion, FSCT cell‐derived ABs inhibited ferroptosis, promoted the macrophage M1‐to‐M2 transition via the miR‐339‐5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.

show abstract

Osteoclast-derived apoptotic bodies show extended biological effects of parental cell in promoting bone defect healing

Cited by 44 publications

References 65 publications

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling

Phospholipid‐Modified Titanium Surface‐Loaded Apoptotic Extracellular Vesicles Promote Early Angiogenesis and Improve Implant Osseointegration Through Immune Regulation

Apoptotic Bodies Derived from Fibroblast‐Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR‐339‐5p/KEAP1/Nrf2 Axis

Contact Info

Product

Resources

About