Extracellular Nucleotides Selectively Induce Migration of Chondrocytes and Expression of Type II Collagen

Szustak, Marcin; Gendaszewska‐Darmach, Edyta

doi:10.3390/ijms21155227

Cited by 8 publications

(4 citation statements)

References 46 publications

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“…S2). Chondrocyte’s migration ability is also known to be essential for cartilage repair [ 36 ]. We found that chondrocytes did not migrate in BM condition at the time point monitored (Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic

Huang,

Zhao,

Lin

et al. 2023

Arthritis Res Ther

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Objective Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA). Methods pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints. Results pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner. Conclusions Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

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Section: Resultsmentioning

confidence: 99%

Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic

Huang,

Zhao,

Lin

et al. 2023

Arthritis Res Ther

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show abstract

“…Inhibition of P2X7R with BBG alleviated the cardiac fibrosis induced by TAC operation in vivo ( Zhou et al, 2020 ). Zheng et al investigated the role of P2Y1R in norepinephrine (NE)-stimulated cardiac fibroblasts, revealed that P2Y1R modulates CFs proliferation via induction of c-fos and inhibition of DNA synthesis ( Zheng et al, 1998 ; Szustak and Gendaszewska-Darmach, 2020 ). In addition, another study reported that A1, A2A, P2Y1R, P2Y11R and P2X7R agonists modulated the TGF-β1-evoked epithelial to mesenchymal transition (EMT) through the PKA and MAPK/ERK signaling pathway ( Zuccarini et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

P2Y1 Receptor Agonist Attenuates Cardiac Fibroblasts Activation Triggered by TGF-β1

et al. 2021

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Cardiac fibroblasts (CFs) activation is a hallmark feature of cardiac fibrosis caused by cardiac remodeling. The purinergic signaling molecules have been proven to participate in the activation of CFs. In this study, we explored the expression pattern of P2Y receptor family in the cardiac fibrosis mice model induced by the transverse aortic constriction (TAC) operation and in the activation of CFs triggered by transforming growth factor β1 (TGF-β1) stimulation. We then investigated the role of P2Y1receptor (P2Y1R) in activated CFs. The results showed that among P2Y family members, only P2Y1R was downregulated in the heart tissues of TAC mice. Consistent with our in vivo results, the level of P2Y1R was decreased in the activated CFs, when CFs were treated with TGF-β1. Silencing P2Y1R expression with siP2Y1R accelerated the effects of TGF-β1 on CFs activation. Moreover, the P2Y1R selective antagonist BPTU increased the levels of mRNA and protein of profibrogenic markers, such as connective tissue growth factor (CTGF), periostin (POSTN). periostin (POSTN), and α-smooth muscle actin(α-SMA). Further, MRS2365, the agonist of P2Y1R, ameliorated the activation of CFs and activated the p38 MAPK and ERK signaling pathways. In conclusion , our findings revealed that upregulating of P2Y1R may attenuate the abnormal activation of CFs via the p38 MAPK and ERK signaling pathway.

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“…E.g., muscarinic receptors display voltage-dependent responses, with depolarizing stimuli enhancing M1-type receptor responses while reducing those of M2 receptors ( Ben-Chaim et al, 2006 ); in chondrocytes, this may lead to increased GAG synthesis ( Lind et al, 1998 ). The ubiquitous P2Y 12 purinergic receptor, present in chondrocytes and involved in their migration ( Szustak and Gendaszewska-Darmach, 2020 ) is another example where voltage sensing through GPCRs may impact function ( Zhang et al, 2020 ).…”

Section: Making Sense Of the Streaming Potential: The Whodunit Of Mem...mentioning

confidence: 99%

A new look at osteoarthritis: Threshold potentials and an analogy to hypocalcemia

Gelder

Audenaert²,

Calders³

et al. 2023

Front. Aging

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Cartilage is a tissue that consist of very few cells embedded in a highly negatively charged extracellular matrix (ECM). This tissue is dealing with several electrical potentials which have been shown to control the production of ECM. Cartilage is present at joints and is constantly prone to degradation. Failing to repair the damage will result in the occurrence of osteoarthritis (OA). This perspective aims to link biophysical insights with biomolecular research in order to provide an alternative view on the possible causes of OA. Firstly, we hypothesize the existence of a threshold potential, which should be reached in order to initiate repair but if not met, unrepaired damage will evolve to OA. Measurements of the magnitude of this threshold electrical potential would be a helpful diagnostic tool. Secondly, since electrical potential alterations can induce chondrocytes to synthesize ECM, a cellular sensor must be present. We here propose an analogy to the hypocalcemia ‘unshielding’ situation to comprehend electrical potential generation and explore possible sensing mechanisms translating the electrical message into cellular responses. A better understanding of the cellular voltage sensors and down-stream signalling mechanisms may lead to the development of novel treatments for cartilage regeneration.

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Extracellular Nucleotides Selectively Induce Migration of Chondrocytes and Expression of Type II Collagen

Cited by 8 publications

References 46 publications

Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic

Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic

P2Y1 Receptor Agonist Attenuates Cardiac Fibroblasts Activation Triggered by TGF-β1

A new look at osteoarthritis: Threshold potentials and an analogy to hypocalcemia

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