Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways

Qi, Hui; Liu, Danping; Xiao, Dawei; Tian, Dachuan; Su, Yongwei; Jin, Shaofeng

doi:10.1007/s11626-019-00330-x

Cited by 92 publications

(79 citation statements)

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“…Here, we further showed signaling pathways of ERK, AKT, mTOR and their phosphorylation in GCs of different size follicles. In the present study, the phosphorylated ERK (p-ERK1/2) in GCs from large follicles was significantly higher than that of GCs from small and medium follicles, which demonstrates that ERK1/2 phosphorylation was increased significantly in apoptotic cells in previously published studies [24,25]. Furthermore, MAPK/ERK1/2 and PI3K/AKT are two signaling pathways that negatively regulate autophagy through the mTOR pathway [26,27].…”

Section: Discussionsupporting

confidence: 65%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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Follicular atresia is closely related to both apoptosis and autophagy of granulosa cells (GCs) in ovarian follicles. In the present study, GCs were isolated from pig ovaries in small, medium and large antral follicles, and the current results showed that the proliferation of GCs was higher in medium follicles, and lower in large follicles compared to small follicles. The Bax and Caspase 3 mRNA levels were significantly higher, but the ratio of Bcl-2/Bax was lower in GCs of large follicles. The marker genes of autophagy, Atg3, Atg7 and LC3 mRNA levels were higher in GCs from medium follicles. Apoptosis- and autophagy-related proteins had a similar expression pattern to the mRNA level. Our results showed that phosphorylated ERK (p-ERK) was activated in GCs of large follicles, while phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were inhibited in GCs of medium follicles. Labeling of autophagic vesicles with 4’,6-diamidino-2-phenylindole (DAPI) and monodansylcadaverine (MDC) confirmed the results of gene transcription and protein expression in GCs of different size follicles. We conclude that autophagy and apoptosis of GCs occurred in different size follicles during follicular development, and autophagy was mainly found in GCs of medium follicles, while apoptosis was mainly found in GCs of large follicles.

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Section: Discussionsupporting

confidence: 65%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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“…As particles naturally secreted from the cell, EV has been identified as vital mediators of paracrine communication (Batiz et al, 2015;Jing et al, 2018) and demonstrated a key role in different processes, such as angiogenesis (Qi et al, 2016), antigen presentation (Shenoda and Ajit, 2016), apoptosis (Qi et al, 2019), coagulation (Fricke et al, 2017), cellular homeostasis (Takahashi et al, 2017), inflammation (Zhang S. et al, 2019).…”

Section: Extracellular Vesicles (Ev) Ev: Definition Classification mentioning

confidence: 99%

“…More recently, MSCs-EV have been shown to mediate the therapeutic effects of MSCs in various diseases and have been applied to clinical trials for several diseases, such as type I diabetes mellitus (trial NCT02138331), macular holes (NCT03437759) and acute ischemic stroke (NCT03384433) 4 . Thus, the role of MSCs-EV in the treatment of bone diseases has Inhibit T lymphocyte proliferation, stimulate macrophage polarization toward anti-inflammatory phenotype, restore mitochondrial function and oxidative stress damage, balance the energy metabolism, suppress mitochondrial dysfunction apoptosis of chondrocytes through inhibiting the phosphorylation of p38 and ERK1/2 c , and stimulating of the phosphorylation of AKT d signaling pathway, which promote cartilage regeneration Chen et al, 2016Chen et al, , 2019Cosenza et al, 2017Cosenza et al, , 2018Mao et al, 2018;Qi et al, 2019 AD a Bone marrow mesenchymal stem cells; b Osteoarthritis; c Extracellular regulated protein kinases; d Phosphorylation of protein-serine-threonine kinase; e Adipose tissuederived mesenchymal stem cells; f Interleukin-1β; g Human embryonic-derived mesenchymal stem cells; h Adenosine 5 -monophosphate (AMP)-activated protein kinase; i Sulfated glycosaminoglycan; j Infrapatellar fat pad (IPFP)-derived mesenchymal stem cells; k Mammalian target of rapamycin; l Synovial mesenchymal stem cells; m Yes-associated protein; n Extracellular matrix; o Rheumatoid arthritis; p Matrix metalloproteinase 14; q Vascular endothelial growth factor; r Human-induced pluripotent mesenchymal stem cells; s Osteoporosis; t Mitogen-activated protein kinase; u DNA methyltransferase1; v Runt-related transcription factor 2; w Alkaline phosphatase;…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

Liu

Liang

et al. 2020

Front. Cell Dev. Biol.

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Bone is crucial for supporting the body, protecting other organs, providing minerals, and secreting hormone to regulate other organ's function. Bone disorders result in pain and disability, severely affecting human health, reducing the quality of life and increasing costs to society. With the rapid increase in the aging population worldwide, bone disorders have become one major disease. As a result, efficacious therapies of bone disorders have become the focus of attention worldwide. Mesenchymal stem cells (MSCs) have been widely explored as a new therapeutic method for numerous diseases. Recent evidence suggests that the therapeutic effects of MSCs are mainly mediated by their extracellular vesicles (EV). MSCs-derived extracellular vesicles (MSCs-EV) is indicated as a novel cell-free alternative to cell therapy with MSCs in regenerative medicine. Here, we review the current knowledge of EV and highlight the application studies of MSCs-EV in bone disorders by focusing on osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP), and bone fracture. Moreover, we discuss the key issues and perspectives of MSCs-EV as a clinical therapeutic strategy for bone diseases.

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“…Zhu et al also revealed that BMSCs derived exosomes could protect chondrocytes from apoptosis and senescence [33] . Furthermore, Qi et al observed the uptake of exosomes from BMSCs by chondrocytes [34] , and exosomes from BMSCs could inhibit mitochondrialinduced apoptosis of chondrocytes in response to IL-1β, with p38, ERK, and Akt pathways involved. Exosomes from embryonic MSC (ESCs) have shown the potential of alleviating matrix degradation and promoting cartilage repair in some animal models [35][36][37] .…”

Section: Exosomes From Different Types Of Mscsmentioning

confidence: 99%

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

et al. 2020

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Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

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Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways

Cited by 92 publications

References 50 publications

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

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