HWJMSC-derived extracellular vesicles ameliorate IL-1β-induced chondrocyte injury through regulation of the BMP2/RUNX2 axis via up-regulation TFRC

Chen, Zhian; Ding, Wei; Duan, Peiya; Lv, XiaoYu; Yan, Feng; Yin, Zhengbo; Zhang, Luo; Li, Zhigui; Zhang, Hua; Zhou, Tian; Tan, Hongbo

doi:10.1016/j.cellsig.2023.110604

Cited by 3 publications

(5 citation statements)

References 74 publications

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“…According to studies, TFRC plays a signi cant role in the formation of OA brought on by iron death. Additionally, because it is an upstream factor of IL-1β, it can further in uence the OA development process by either activating iron death or upregulating IL-1β [42,43,44] . As HEPH plays a crucial role in the intestinal transport of iron ions, it keeps cellular iron from building up and shields cells from iron-induced oxidative stress by inhibiting the overexpression of iron ions and their excretion through the intestines [45] ,and copper ion de ciency can lead to a decrease in HEPH protein oxidase activity thereby reducing the binding of iron ions [46] .…”

Section: Discussionmentioning

confidence: 99%

Identification of copper metabolism-related biomarkers and exploration of mechanisms based on osteoarthritis transcriptomics data

He,

Wang,

Zheng

et al. 2023

Preprint

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Background Studies have demonstrated that copper metabolism related genes (CMRGs) are tightly associated with a high risk of developing osteoarthritis (OA). However, the details of their regulation are not well understood. Hence, this research intends to explore the mechanism of CMRGs in OA and to provide new clues for the treatment of OA. Methods The GSE48556 and GSE63359 datasets were sourced from the Gene Expression Omnibus (GEO) database. The 133 CMRGs were collected from the literature. Differentially expressed genes (DEGs) between case and control cohorts in the GSE48556 dataset were identified through differentially expressed analysis. Moreover, differentially expressed-CMRGs (DE-CMRGs) were gained via overlapping DEGs and CMRGs. Then, we performed gene enrichment analysis for the DE-CMRGs to identify their regulatory functions. The DE-CMRGs with consistent and markedly divergent expression trends in both datasets were considered as biomarkers. Subsequently, we verified the results using real-time reverse transcription-PCR (qRT-PCR) in clinical blood specimen. Receiver Operating Characteristic (ROC) curves were mapped to assess the predictive accuracy. Finally, Gene Set Enrichment Analysis (GSEA), the Gene-Gene Interaction (GGI) network, immune-related function, and drug prediction were executed, then correlations between biomarkers as well as between biomarkers and immune-related pathways or cells were determined. Results Totally, 4,325 DEGs and 32 DE-CMRGs were selected in GSE48556 dataset, and functional enrichment analysis showed that they were involved in ‘response to copper ion’ and ‘copper ion binding’, which were consistent with the path of our research. KEGG, GSEA and GGI outcomes indicated that there were mainly involved in the pathways of ‘olfactort transduction’, ‘iron ion transport’, ‘ferroptosis’, ‘platinum drug resistance’ and so on. Through simultaneous screening of both datasets, four biomarkers (APP, CUTC, TFRC, and HEPH) were discovered. Then, all of area under curves (AUC) values of the ROC curves exhibited strong prediction accuracy. APP, CUTC and TFRC plasma levels were significantly higher in OA patients compared to controls (p < 0.05). However, the HEPH plasma level of OA patients was significantly decreased compared to controls (P < 0.01). According to correlation analysis, HEPH was positively connected with Th1 cells and the CCR immune path, and negatively correlated with APP, Th2 cells, and the check-point immune pathway. There were 35 drugs predicted by 4 biomarkers such as L-methionine (R)-S-oxide, Mercuribenzoic Acid and Copper. The expression levels of APP, CUTC, and TFRC genes in plasma of OA patients were dramatically lowered (P < 0.05) compared to the control, while the expression levels of HEPH genes were significantly elevated (P < 0.01). Conclusion Four biomakers (APP, CUTC, TFRC, and HEPH) were identified as CM biomarkers in OA, which offered a fresh standpoint to probe the connection between CMRGs and OA.

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Section: Discussionmentioning

confidence: 99%

Identification of copper metabolism-related biomarkers and exploration of mechanisms based on osteoarthritis transcriptomics data

He,

Wang,

Zheng

et al. 2023

Preprint

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“…HWJMSC-EVs were isolated as described previously [16]. Ribo ™ Exosome Isolation Reagent (Ribobio, China) was used to isolate EVs.…”

Section: Isolation Of Hwjmsc-evsmentioning

confidence: 99%

“…PKH67 immunofluorescence staining was performed as described previously [16]. Briefly, hWJMSC-EV-treated hBMSCs and chondrocytes were fixed in 4% paraformaldehyde for 15 min and permeabilized.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

“…2A and B, co-culture with hWJMSCs promoted the viability of hBMSCs and chondrocytes, but resulted in no differences in cellular morphology. Because our previous study found that hWJMSCs-EVs alleviated IL-1β-induced chondrocyte damage [16], the hWJMSCs-EVs were isolated to investigate the effect of hWJMSCs-EVs on the viability of hBMSCs and chondrocytes. The results showed that hWJMSCs-EVs promoted the vitality of hBMSCs and chondrocytes, but the phenomenon was suppressed by an exosome inhibitor (GW4869; 10 μm) (Fig.…”

Section: Hwjmscs and Hwjmsc-evs Promoted The Activity Of Hbmscs And C...mentioning

confidence: 99%

“…Depending on their source, EVs contain different DNA, RNA, lipids, metabolites, and cytosolic and cell surface proteins [11], and can undergo intercellular signaling and alter the biological activity of recipient cells through their own substances [12,13]. Based on extensive research [14,15], previous experiments have shown that human umbilical cord Wharton's jelly mesenchymal stem cell (hWJMSC)derived EVs (hWJMSC-EVs) have significant effects in inhibiting chondrocyte apoptosis, improving chondrocyte viability, and promoting cell cycle progression [16]. Furthermore, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) achieve tissue regeneration by regulating transforming growth factor (TGF)-β [17] in spinal cord injury [18], kidney disease [19], osteochondral injury, and osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

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HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

Chen,

Zhou,

Luo

et al. 2024

J Nanobiotechnol

Self Cite

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The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery. Graphical abstract

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Application of mesenchymal stem cells derived from the umbilical cord or Wharton’s jelly and their extracellular vesicles in the treatment of various diseases

Patel,

Mohamed,

Rizaev

et al. 2024

Tissue and Cell

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HWJMSC-derived extracellular vesicles ameliorate IL-1β-induced chondrocyte injury through regulation of the BMP2/RUNX2 axis via up-regulation TFRC

Cited by 3 publications

References 74 publications

Identification of copper metabolism-related biomarkers and exploration of mechanisms based on osteoarthritis transcriptomics data

Identification of copper metabolism-related biomarkers and exploration of mechanisms based on osteoarthritis transcriptomics data

HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

Application of mesenchymal stem cells derived from the umbilical cord or Wharton’s jelly and their extracellular vesicles in the treatment of various diseases

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