Ivabradine abrogates TNF-α-induced degradation of articular cartilage matrix

Xiang, Xianxiang; Zhou, Yunfei; Sun, Honglin; Tan, Shiping; Lu, Zhanbin; Huang, Lixin; Wang, Weiming

doi:10.1016/j.intimp.2018.11.035

Cited by 14 publications

(13 citation statements)

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“…Therefore, exploring better OA treatment methods has been a research focus in the field of orthopedics. Although the pathogenesis of OA is unclear, it is generally believed that OA is associated with increased proinflammatory cytokines, activation of inflammation-associated signaling pathways, and the degradation of the extracellular matrix (ECM) (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Quercetin suppresses apoptosis of chondrocytes induced by IL‑1β via inactivation of p38 MAPK signaling pathway

Wang

Xie

et al. 2021

Exp Ther Med

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The objective of the present study was to investigate the effect of quercetin and evaluate its protective effect on articular cartilage in patients with osteoarthritis (OA), by intervening the p38 pathway. The target factors of quercetin protecting articular cartilage in patients with OA were predicted scientifically and analyzed to predict the possible pathways by using network pharmacology. A pathway predicted to be closely associated with osteoarthritis was chosen for experimental verification in in vitro cells. The optimal intervention drug concentrations were selected by the of Cell Cycle Kit-8 assay, osteoarthritis and inflammatory factors relevant to osteoarthritis, interleukin-1β and tumor necrosis factor-α, were tested by of enzyme-linked immunosorbent assay, and the expression of relevant proteins and mRNA of the p38 signaling pathway was tested by reverse transcription-quantitative PCR and western blotting, following quercetin intervention. It was found that quercetin, at the concentration of 100 umol/l, can decrease inflammatory factors relevant to OA, inhibit the expression of p38, matrix metalloprotease 13 and ADAMTS in the pathway, and promote the expression of collagen Ⅱ. Therefore, it is postulated that quercetin can lower the expression of inflammatory factors in cartilage for the prevention and treatment of OA, and the expression level of relevant factors can be changed positively by blocking the p38 MAPK signaling pathway. Thus, quercetin can promote the repair of degenerative chondrocytes and protect articular chondrocytes.

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Section: Introductionmentioning

confidence: 99%

Quercetin suppresses apoptosis of chondrocytes induced by IL‑1β via inactivation of p38 MAPK signaling pathway

Wang

Xie

et al. 2021

Exp Ther Med

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“…The variety of ion channel inhibitors, abundantly and protractedly used to treat CVD, are likely to modulate ion channel-mediated events in chondrocytes, which in turn affects their metabolism, osmotic responses, turnover of cartilage ECM and inflammatory responses. The HCN channel inhibitor ivabradine had cartilage-ECM production stimulating responses in vitro [130]. Members of the β-adrenoreceptor inhibitors group may diminish adrenergic system-related adverse effects on chondrogenesis, such as reduced ECM production [186], while angiotensin-aldosterone system modulators (captopril, enalapril, losartan) showed both stimulatory and inhibitory effects in cartilage regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Ivabradine inhibits HCN channels and decreases K + flow to extracellular space, which changes membrane potential and shortens the depolarisation phase in the myocyte membrane, causing bradycardia (Figure 5). Protective effects of ivabradine on TNF-α-treated primary human chondrocytes were observed [130]. Ivabradine also restored SERCA activity after myocardial infarction in rats [173].…”

Section: Hyperpolarization-activated Cyclic Nucleotide-gated (Hcn) Channelsmentioning

confidence: 93%

“…ycardia (Figure 5). Protective effects of ivabradine on TNF-α-treated primary human chondrocytes were observed [130]. Ivabradine also restored SERCA activity after myocardial infarction in rats [173].…”

Section: Hyperpolarization-activated Cyclic Nucleotide-gated (Hcn) Channelsmentioning

confidence: 93%

“…The authors also showed that ivabradine inhibited the activation of NF-κB, which was elevated in patients with OA and had analgesic, anti-inflammatory and antioxidant properties. In addition, ivabradine reduced inflammation caused by TNF-α in human primary chondrocytes by diminishing levels of IL-6 and IL-1β [130]. Thus, HCN inhibitors seem to have complex activity, which can positively affect human chondrocytes and cartilage.…”

Section: Hyperpolarization-activated Cyclic Nucleotide-gated (Hcn) Channelsmentioning

confidence: 98%

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Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels

Vaiciuleviciute

Bironaitė

Uzielienè

et al. 2021

Cells

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Osteoarthritis (OA) and cardiovascular diseases (CVD) share many similar features, including similar risk factors and molecular mechanisms. A great number of cardiovascular drugs act via different ion channels and change ion balance, thus modulating cell metabolism, osmotic responses, turnover of cartilage extracellular matrix and inflammation. These drugs are consumed by patients with CVD for many years; however, information about their effects on the joint tissues has not been fully clarified. Nevertheless, it is becoming increasingly likely that different cardiovascular drugs may have an impact on articular tissues in OA. Here, we discuss the potential effects of direct and indirect ion channel modulating drugs, including inhibitors of voltage gated calcium and sodium channels, hyperpolarization-activated cyclic nucleotide-gated channels, β-adrenoreceptor inhibitors and angiotensin-aldosterone system affecting drugs. The aim of this review was to summarize the information about activities of cardiovascular drugs on cartilage and subchondral bone and to discuss their possible consequences on the progression of OA, focusing on the modulation of ion channels in chondrocytes and other joint cells, pain control and regulation of inflammation. The implication of cardiovascular drug consumption in aetiopathogenesis of OA should be considered when prescribing ion channel modulators, particularly in long-term therapy protocols.

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