miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis

Wu, Jiangyi; Kuang, Liang; Chen, Cheng; Yang, Junjun; Zeng, Wei‐Nan; Li, Tao; Chen, Hao; Huang, Shao-Lun; Fu, Zhenlan; Li, Jiamiao; Liu, Renfeng; Ni, Zhenhong; Chen, Lin; Yang, Liu

doi:10.1016/j.biomaterials.2019.03.022

Cited by 416 publications

(404 citation statements)

References 76 publications

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“…They contain many biologically active substances secreted by recipient cells, such as noncording RNA (ncRNA), proteins, and mRNA. And it plays an important role in the extracellular microenvironment and intercellular communication [12,[15][16][17][18]. Kato [19] extracted exosomes from the supernatant of IL-1β-induced synovial fibroblasts and then added exosomes to chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that synovial tissue may regulate chondrocytes by secreting exosomes. Number of articles [15][16][17][18][19][20][21][22] has conducted detailed studies on how to extract cell supernatants and exosomes in body fluids, but few of articles had studied the extraction and identification of exosomes in tissues. To the best of our knowledge, any article has been published on how to extract and identify exosomes from synovial tissue.…”

Section: Introductionmentioning

confidence: 99%

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Extraction and identification of synovial tissue-derived exosomes by different separation techniques

et al. 2020

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Objective: The aim of this study is to compare the efficiency of different separation techniques for extracting synovial tissue-derived exosomes. Methods: The synovial tissue discarded during knee arthroscopy or total knee arthroplasty surgery was collected from the Third Affiliated Hospital of Beijing University of Chinese Medicine. Ultracentrifugation (UC), filtration combined with size exclusion chromatography (SECF), and 8% polyethylene glycol (PEG) were used to extract synovial tissue-derived exosomes. Transmission electron microscopy (TEM), nanoparticle tracer analysis (NTA), and Western Blot (WB) were used to detect the morphology, particle size, and biomarker proteins (CD9, CD63, Flotillin-1, and calnexin) of exosomes. Results: The extracts of enriched round and discoid vesicles were successfully extracted with UC, SECF, and PEG. The results of TEM have shown that all three extraction methods can extract circular or elliptical vesicles with discand cup-shaped structures from the synovial tissue, with the diameter is about 30-150 nm. NTA suggested the main peaks of three groups of exosomes are around 100-120 nm, and the concentration of the three groups of exosomes was greater than 1 × 10 10 /ml. The results of WB showed that three positive protein markers (CD9, CD63, and Flotillin-1) were highly expressed in the suspension extracted by the three methods and low in the synovial tissue. However, the negative protein (calnexin) was highly expressed in synovial tissues and PEG group, while low in UC and SECF group. Conclusion: Morphology, particle size, and labeled protein marker detection confirmed that UC, SECF, and PEG can extract exosomes derived from synovial tissue; UC and SECF are more recommended for the extraction of synovial tissue-derived exosomes, which provides a methodological basis for studying the function and mechanism of synovial tissue exosomes in the future.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

et al. 2020

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“…Nonetheless, the screening and confirmation of candidate factors participating in the chondrogenic enhancement observed with PCM is far from complete. In addition, the possible role of exosomal CD73-mediated adenosine activation of AKT, ERK, and AMPK signaling [14,64] and the participation of exosomal microRNAs [65,66] that have been previously implicated in regulating chondrocyte anabolic activity and cartilage degradation have yet to be examined. Further work will be required to fully decipher the paracrine mechanisms responsible for the enhanced anabolic and protective effect observed here in response to PCM administration, including the examination of the contribution of EVs to our reported PEMF-mediated secretome responses.…”

Section: Discussionmentioning

confidence: 99%

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

et al. 2020

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Background: The mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are "environmentally responsive" to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.Methods: Conditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.Results: We show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis. Conclusions:The findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.

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“…The chondroprotection role could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. In other study, Wu et al attributed the cartilage protection of exosomes from ASCs to the high level of exosomal miR-100-5p [40] , because the exosomal miR-100-5p could bind to the 3′-untranslated region (3'UTR) of mTOR, then significantly enhance autophagy level in OA chondrocytes via mTOR inhibition.…”

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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miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis

Cited by 416 publications

References 76 publications

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

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

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