Vascular endothelial cell-secreted exosomes facilitate osteoarthritis pathogenesis by promoting chondrocyte apoptosis

Yang, Runze; Zheng, Huo‐Liang; Xu, Wen-Ning; Zheng, Xianxu; Li, Bo; Jiang, Lei‐Sheng; Jiang, Sheng‐Dan

doi:10.18632/aging.202506

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…This method effectively maintained cellularity, especially for rare cells, including endothelial cells, and allowed exploring the transcriptome of meniscus endothelial cells in a highthroughput manner. Indeed, clarifying the genetic features of meniscus endothelial cells will help gain insights into the development of OA [33] and cultivate new strategies against this disease. Normally, two feature genes were adopted to identify specific cell types; however, in this study, three feature genes (CD93, CDH5, and PECAM1) were used to isolate meniscus endothelial cells for downstream analysis, making it more reliable.…”

Section: Discussionmentioning

confidence: 99%

Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

Wei

Chen

et al. 2022

Disease Markers

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Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.

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Section: Discussionmentioning

confidence: 99%

Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

Wei

Chen

et al. 2022

Disease Markers

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“…Synovial fluid-derived EVs recruited inflammatory cells and inhibited cartilage proliferation, promoting joint degeneration [ 12 ]. EVs derived from vascular endothelial cells reduced the ability of chondrocytes to resist oxidative stress by inhibiting autophagy and p21 expression, thereby increasing cell ROS content and inducing cell apoptosis [ 13 ]. Wu et al found that EVs derived from sclerotic osteoblasts inhibited the synthesis of the extracellular matrix (ECM) of chondrocytes and reduced the expression of chondrocyte-specific markers, and it is proved that miR-210-5p in EVs inhibited the oxygen consumption rate of chondrocytes and changed their bio-energy state, as often observed under OA conditions [ 14 ].…”

Section: The Role and Diagnostic Potential Of Ev In The Progression Of Oamentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

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“…39 Yang et al showed that exosomes derived from vascular ECs promoted the progression of OA by promoting chondrocyte apoptosis. 40 Therefore, we speculate that pre-ECs in OA may allow for bone formation through exosomes digesting cartilage and promote subchondral bone remodelling through IL-mediated inflammation. The characterisation of these two novel subsets improves our understanding of the characteristics and functions of ECs in the OA subchondral bone.…”

Section: Discussionmentioning

confidence: 92%

Single-cell RNA-sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the development of osteoarthritis

Yan

Cui

Liu

et al. 2022

Preprint

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The cellular composition and underlying spatiotemporal transformation processes of subchondral bone in osteoarthritis (OA) remain unknown. Herein, various cell subsets from tibial plateau of OA patients are identified, and the mechanism of subchondral microstructure alteration is elaborated using single-cell RNA sequencing technique. We identified two novel endothelial cell (EC) populations characterized by either exosome synthesis and inflammation response, or vascular function and angiogenesis. Three osteoblast (OB) subtypes are introduced, separately related to vascularization, matrix manufacturing and matrix mineralization. The distinct roles and functions of these novel phenotypes in OA development are further discussed, as well as interaction network between these subpopulations. The variation tendency of each population is testified in a DMM mouse model. The identification of cell types demonstrates a novel taxonomy and mechanism for ECs and OBs inside subchondral bone area, provides new insights into the physiological and pathological behaviors of subchondral bone in OA pathogenesis.

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Vascular endothelial cell-secreted exosomes facilitate osteoarthritis pathogenesis by promoting chondrocyte apoptosis

Cited by 21 publications

References 37 publications

Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

Single-cell RNA-sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the development of osteoarthritis

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