Characterization of the Proinflammatory Profile of Synovial Fluid-Derived Exosomes of Patients with Osteoarthritis

Domenis, Rossana; Zanutel, Rossella; Caponnetto, Federica; Toffoletto, Barbara; Cifù, Adriana; Pistis, Cinzia; Benedetto, P. Di; Causero, Araldo; Pozzi, Massimo; Bassini, F; Fabris, Martina; Niazi, Kayvan; Soon‐Shiong, Patrick; Curcio, Francesco

doi:10.1155/2017/4814987

Cited by 88 publications

(69 citation statements)

References 36 publications

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“…Although the concentration of exosomes purified by immunoaffinity (1.5 ± 1.2 × 10 11 particles/ml) was significantly lower than the concentration from polymer precipitation (7.6 ± 3.1 × 10 11 particles/ml), the size distribution of the immunoaffinity method (diameter: 88.01 ± 25.5 nm, range: 55.5-125.9 nm) was significantly more restricted, at 30 to 100 nm, than from the polymer precipitation method (diameter: 144.4 ± 22.2 nm, range 124-187.9 nm). After isolation with Exoquick polymer precipitation, contamination by immune complexes was detected, requiring magnetic beadbased purification [15]. This finding indicated that the immunoaffinity purification method has higher accuracy and less contamination than the polymer precipitation method.…”

Section: Isolation and Verification Of Exosomesmentioning

confidence: 99%

“…Identifying an optimal method to purify exosomes for downstream functional, biomarker or therapeutic studies is important. Domenis et al compared two methods for exosome isolation from synovial fluid (SF), Exoquick polymer precipitation and immunoaffinity purification [15]. Although the concentration of exosomes purified by immunoaffinity (1.5 ± 1.2 × 10 11 particles/ml) was significantly lower than the concentration from polymer precipitation (7.6 ± 3.1 × 10 11 particles/ml), the size distribution of the immunoaffinity method (diameter: 88.01 ± 25.5 nm, range: 55.5-125.9 nm) was significantly more restricted, at 30 to 100 nm, than from the polymer precipitation method (diameter: 144.4 ± 22.2 nm, range 124-187.9 nm).…”

Section: Isolation and Verification Of Exosomesmentioning

confidence: 99%

“…Therefore, most studies about mechanisms of joint diseases focused on exosomes derived from synovial fibroblasts or SF. Domenis et al investigated the immune regulatory properties of SF-derived exosomes of end-stage OA patients on macrophages differentiated from human peripheral blood mononuclear cells (PBMCs) [15]. After treatment with exosomes, macrophages were found to produce a spectrum of pro-inflammatory cytokines and chemokines, including MMP12, MMP7, IL-1β, CCL8, CCL15, [17].…”

Section: Physiological and Pathological Effects Of Exosomes In Joint mentioning

confidence: 99%

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Emerging Role of Exosomes in the Joint Diseases

Zeng

Wang

et al. 2018

Cell Physiol Biochem

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Exosomes are a subset of small, membrane-bound extracellular vesicles that are important for communication among cells. They originate from the cell membrane during endocytic internalization, and are stable in biological fluids, including blood and synovial fluids. Increasing knowledge is emerging about exosomes in joint diseases, including osteoarthritis, rheumatoid arthritis, osteonecrosis of the femoral head, and others. Exosomes in synovial fluid can lead to inflammation, degeneration of cartilage, and destruction of joints. Exosomes in blood have diagnostic value in the early disease stage or for complicated conditions of joint diseases. Exosomes from stem cells could delay diseases and repair joints. For a comprehensive understanding about the emerging role of exosomes in joint diseases, we introduced the isolation and verification of exosomes from synovial fluid, reviewed the physiological and pathological effects of exosomes on joints, and discussed the diagnostic value and therapeutic potential of exosomes in joint diseases. In the future, immunologically active exosomes and engineered exosomes will of interest in the joint diseases. Challenges in the field of exosomes in joint-disease research include complex and expensive isolation, detection of contributing molecular, effectiveness and safety evaluation. In summary, challenges remain, but the field of exosomes in joint diseases has potential, including in mechanisms, diagnoses and therapies.

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Section: Isolation and Verification Of Exosomesmentioning

confidence: 99%

Section: Isolation and Verification Of Exosomesmentioning

confidence: 99%

Section: Physiological and Pathological Effects Of Exosomes In Joint mentioning

confidence: 99%

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Emerging Role of Exosomes in the Joint Diseases

Zeng

Wang

et al. 2018

Cell Physiol Biochem

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“…showed that exosomes derived from IL‐1β–stimulated synovial fibroblasts significantly upregulated the expression of proteolytic enzymes MMP‐13 and ADAMTS5, while downregulating the expression of cartilage matrix proteins COL2A1 and aggrecan in normal articular chondrocytes and in cartilage explants . Exosomes derived from the synovial fluid of OA patients stimulated the release of proinflammatory factors from M1 macrophages . Moreover, articular chondrocytes treated with exosomes derived from the synovial fluid of OA patients had decreased expression of anabolic genes and elevated expression of catabolic and inflammatory genes, suggesting a pathologic role for these exosomes in OA progression …”

Section: Exosomes: Basic Biologymentioning

confidence: 99%

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration

Cobelli

Leong

Sun

2017

Annals of the New York Academy of Sciences

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Exosomes are nanovesicles secreted from cells that play key roles in intercellular communication. They carry unique content derived from parental cells and are capable of transferring this cargo between cells. The role and function of exosomes largely depends on the origin and functional status of the parental cells. Emerging evidence indicates that exosomes are associated with biological processes and pathogenesis of certain diseases. These nanovesicles offer great potential as biomarkers, enabling the monitoring and diagnosis of various diseases in a noninvasive manner. Furthermore, as an efficient vehicle of biomolecular intercellular transfer, exosomes are under intensive investigation for their potential for drug delivery and carriers for gene therapy. Here, we first summarize the basic biology and function of exosomes, followed by a discussion of their clinical potential, including the use of exosomes for disease diagnosis, treatment, and drug delivery. The review will highlight the potential of exosomes derived from stem cells in regenerative medicine, with a focus on musculoskeletal tissues. We conclude by sharing our views on the challenges, opportunities, and future directions for the use of exosomes as a therapeutic treatment for the repair and regeneration of musculoskeletal tissues.

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“…Through communication between joint cells, EVs may modulate gene expression and change downstream functions of recipient cells, as well as physiological or pathological processes. For example, synovial fibroblast‐derived EVs from osteoarthritis (OA) patients stimulate macrophages to produce a spectrum of proinflammatory cytokines and chemokines, which leads to a further acceleration of cartilage degradation . In contrast, EVs released from MSCs have been suggested to have therapeutic properties and inhibit cartilage degradation and inflammation in OA .…”

mentioning

confidence: 99%

Extracellular Vesicles Released From Articular Chondrocytes Play a Major Role in Cell–Cell Communication

Liu

Shortt

Zhang

et al. 2019

Journal Orthopaedic Research

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The purpose of this investigation was to determine the role of extracellular vesicles (EVs), released from articular chondrocytes in a physiological or pathological state, in cell–cell communication with other articular chondrocytes or chondrocyte precursor cells. The conditioned medium from interleukin‐1β (IL‐1β)‐treated human articular chondrocytes stimulated catabolic events and inhibited type II collagen expression in articular chondrocytes to a much greater degree than medium from IL‐1β‐treated chondrocytes after complete removal of EVs. The vehicle‐treated and IL‐1β‐treated human articular chondrocytes released EVs of similar size; however, the number of EVs released by IL‐1β‐treated chondrocytes was markedly higher than the number of EVs released from the vehicle‐treated cells. Furthermore, our findings demonstrate that similar to medium from IL‐1β‐treated chondrocytes containing EVs, EVs isolated from medium of IL‐1β‐treated chondrocytes stimulated catabolic events in articular chondrocytes, whereas EVs isolated from the medium of vehicle‐treated chondrocytes inhibited catabolic events and increased messenger RNA levels of aggrecan and type II collagen in IL‐1β‐treated chondrocytes. Furthermore, the medium containing EVs from vehicle‐treated articular chondrocytes or EVs isolated from this medium stimulated chondrogenesis of C3H10T1/2 cells, whereas medium containing EVs from IL‐1β‐treated chondrocytes or EVs isolated from this medium inhibited chondrogenesis. Our findings suggest that EVs released by articular chondrocytes play a key role in the communication between joint cells and ultimately in joint homeostasis, maintenance, pathology, and repair. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:731‐739, 2020

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Characterization of the Proinflammatory Profile of Synovial Fluid-Derived Exosomes of Patients with Osteoarthritis

Cited by 88 publications

References 36 publications

Emerging Role of Exosomes in the Joint Diseases

Emerging Role of Exosomes in the Joint Diseases

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration

Extracellular Vesicles Released From Articular Chondrocytes Play a Major Role in Cell–Cell Communication

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