Schwann Cell-derived exosomes promote bone regeneration and repair by enhancing the biological activity of porous Ti6Al4V scaffolds

Wu, Zhigang; Pu, Panjun; Su, Zhi; Zhang, Xingchang; Nie, Linyang; Chang, Yao-Ming

doi:10.1016/j.bbrc.2020.07.094

Cited by 45 publications

(35 citation statements)

References 14 publications

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“…Adding exosomes to BMSCs for osteogenic induction can increase the expression level of Runx2 and the activity of ALP. In addition, glial cell-derived exosomes in the peripheral nervous system can promote the migration, proliferation, and differentiation of BMSCs, which can effectively improve the efficacy of titanium alloy scaffolds in bone repair ( Wu Z. et al, 2020 ). Tofino-Vian et al (2017) found that exosomes of adiposite-derived stem cells (ASCs) can resist the increased expression of IL-6 and matrix metalloproteinases induced by oxidative stress in osteoarthritis, and play an antioxidant and anti-inflammatory role in osteoarthritis.…”

Section: Regulation Of Bone Marrow Mesenchymal Stem Cells By Exosomes From Extra-skeletal Organsmentioning

confidence: 99%

Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells

Wang

Zhao

et al. 2021

Front. Cell Dev. Biol.

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Exosomes are membranous lipid vesicles fused with intracellular multicellular bodies and then released into the extracellular environment. They contain various bioactive substances, including proteins, mRNA, miRNAs, lncRNAs, circRNAs, lipids, transcription factors, and cytokine receptors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts, chondrocytes, adipocytes, and biological functions. This study provides a theoretical basis for the application of exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) in osteology, exploring different sources of exosomes to improve bone microenvironment and resist bone metastasis. We also provided new ideas for the prevention and rehabilitation of human diseases by exosomes.

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Section: Regulation Of Bone Marrow Mesenchymal Stem Cells By Exosomes From Extra-skeletal Organsmentioning

confidence: 99%

Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells

Wang

Zhao

et al. 2021

Front. Cell Dev. Biol.

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“…Titanium and titanium alloys are the most widely used metal materials in orthopedic clinical implants due to the good properties of titanium ( Szuhanek et al, 2020 ). In the application of internal implants, whether BMSCs on the surface of titanium prosthesis can differentiate into osteoblasts is one of the most critical issues determining the osseointegration effect ( Wu et al, 2020 ). Previous studies have shown that the modification or fixation of surface coatings and biological functional molecules will facilitate osseointegration.…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, HAT transfers the acetyl group of acetyl-CoA to the specific lysine residue at the amino terminus of histones, loosening the chromatin structure and promoting transcription of the gene ( Han et al, 2016 ). Previous literature has reported that HAT played an important role in bone formation and bone loss ( Szuhanek et al, 2020 ; Wu et al, 2020 ). H3K9 is prone to be acetylated and is a key site for acetylation modification ( Zhang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Liu

Cheng

Zhao

et al. 2021

Front. Bioeng. Biotechnol.

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Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

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“…Then again they were collected; next 30 min with 10,000 × g. The supernatant was transferred into the 8.9 mL centrifugal tube (Beckman, USA) to ultracentrifugation at 100,000 × g for 70 min twice at 4°C to get the exosomes. Our extraction method was the same as described in the previous study [ 27 ]. After sucking out all the supernatant, the precipitate was dissolved in 200 μ L PBS and collected in 1.5 mL centrifuge tube for follow-up experiments.…”

Section: Methodsmentioning

confidence: 99%

Paeoniflorin Effect of Schwann Cell-Derived Exosomes Ameliorates Dorsal Root Ganglion Neurons Apoptosis through IRE1α Pathway

Zhu

Han

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes but its pathogenesis is not fully clarified. Endoplasmic reticulum (ER) stress has been confirmed to be involved in the development of DPN. Dorsal root ganglion neuron (DRGn) is the target cell of DPN injure in the peripheral neurons system. Schwann cell (SCs)-derived exosomes (SC-EXOs) can carry IRE1α signal transduction factors in ER stress to DRGn. The aim of this study is to investigate the effect of SC-EXOs treated with paeoniflorin (PF) on DRGn stimulated by high glucose. Methods. SCs were divided into Control group (Control), 150 mM glucose group (HG), high osmotic pressure group (HOP), and low, middle, and high dose PF group (PF1, PF10, and PF100). Exosomes were obtained from SCs by ultracentrifugation and identified according to marker proteins, including CD63, Alix, Hsp70, and TSG101. ER stress initiating factor GRP78, the IRE1α pathway information transmission factor IRE1α, and the phosphorylation level of IRE1α were detected by Western blot, DRGn is divided into Control group (Control), 50 mM glucose group + Control exosomes group (HG + EXOs Control), 50 mM glucose group (HG), and 50 mM glucose group + administration exosomes group (HG + EXOs PF1, HG + EXOs PF10, and HG + EXOs PF100); ER morphology of primary DRGn was observed by using the transmission electron microscope, the level of DRGn apoptosis was analyzed by TUNEL, and the downstream proteins of ER stress including CHOP, XBP1S, JNK, and p-JNK in DRG and the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and Caspase-12 were measured by Western blot. Results. Compared with the exosomes in the HG group, the exosomes after the intervention of PF can significantly reduce the expression of GRP78, IRE1α, and the phosphorylation level of IRE1α P < 0.05 ; compared with the DRGn in the HG group, the SC-EXOs treated with PF could regulate the expression of proteins downstream of IRE1α pathway in ER stress ( P < 0.05 or P < 0.01 ), improve the morphological integrity of ER, and reduce apoptosis in DRGn ( P < 0.05 or P < 0.01 ). Conclusion. PF regulates the information of ER stress carried by SC-EXOs and further affects downstream of IRE1α pathway in DRGn, thus reducing ER stress-induced apoptosis. PF can interfere with DPN through affecting information communication carried by EXOs between SCs and DRGn.

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Schwann Cell-derived exosomes promote bone regeneration and repair by enhancing the biological activity of porous Ti6Al4V scaffolds

Cited by 45 publications

References 14 publications

Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells

Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Paeoniflorin Effect of Schwann Cell-Derived Exosomes Ameliorates Dorsal Root Ganglion Neurons Apoptosis through IRE1α Pathway

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