Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model

Xu, Bo; Xing, Runlin; Huang, Zhengquan; Yin, Songjiang; Li, Xiaochen; Zhang, Li; Ding, Liang; Wang, Peimin

doi:10.1016/j.lfs.2019.05.003

Cited by 56 publications

(49 citation statements)

References 28 publications

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“…i. For immunohistochemistry-paraffin (IHC-P), 4-μm-thick sections of E. multilocularis metacestodes and mouse livers were processed to evaluate the expression of CaM or CaMKII, as described previously [32,33]; immunostaining was performed using rabbit anti-CaM/CaMKII antibodies (Bioss; Beijing) at 1:300/1:200 dilution and secondary antibodies (goat anti-rabbit immunoglobulin G; Bioss) at 1:800 dilution. Finally, the slides were imaged under a fluorescence microscopy (Olympus, Japan).…”

Section: Analysis Of Cam and Camkii Protein Expression Analysis By Immentioning

confidence: 99%

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model

et al. 2021

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Background Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. Methods The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. Results In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 μg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. Conclusions Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.

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Section: Analysis Of Cam and Camkii Protein Expression Analysis By Immentioning

confidence: 99%

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model

et al. 2021

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“…This will eventually lead to chondrocyte apoptosis or inhibition of proliferation. 40 On the other hand, TRPV4 itself can affect the condition of the cartilage matrix to regulate indirectly. It also promotes the expression of A disintegrin and metalloprotease 10 to make CD44 cleavage, resulting in abnormal hyaluronic acid metabolism and matrix stiffness changes.…”

Section: Mechanically Sensitive Ion Channelsmentioning

confidence: 99%

The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage

Jin

et al. 2020

J Orthop Surg (Hong Kong)

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Biomechanical factors play an extremely important role in regulating the function of articular chondrocytes. Understanding the mechanical factors that drive chondrocyte biological responses is at the heart of our interpretation of cascade events leading to changes in articular cartilage osteoarthritis. The mechanism by which mechanical load is transduced into intracellular signals that can regulate chondrocyte gene expression remains largely unknown. The mechanically sensitive ion channel (MSC) may be one of its specific mechanisms. This review focuses on four ion channels involved in the mechanotransduction of chondrocytes, exploring their properties and the main factors that activate the associated pathways. The upstream and downstream potential relationships between the protein pathways were also explored. The specific biophysical mechanism of the chondrocyte mechanical microenvironment is becoming the focus of research. Elucidating the mechanotransduction mechanism of MSC is essential for the research of biophysical pathogenesis and targeted drugs in cartilage injury-related diseases.

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“…The membrane strain induced by hypotonic solution was found to activate the TRPV4 channel, and mechanically induced Ca 2+ influx and SOX9 transcription are associated with the synthesis of articular cartilage [29,30,103]. Membrane stretching activates TRPV4 ion channels and induces Ca 2+ influx in rat articular chondrocytes [104]. TRPV4 ion channels play a role in chondrocyte pathological processes induced by injurious levels of loading [105].…”

Section: Mechanical Responses Of Trp Family Channels In Chondrocytesmentioning

confidence: 98%

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

et al. 2021

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Articular cartilage consists of an extracellular matrix including many proteins as well as embedded chondrocytes. Articular cartilage formation and function are influenced by mechanical forces. Hind limb unloading or simulated microgravity causes articular cartilage loss, suggesting the importance of the healthy mechanical environment in articular cartilage homeostasis and implying a significant role of appropriate mechanical stimulation in articular cartilage degeneration. Mechanosensitive ion channels participate in regulating the metabolism of articular chondrocytes, including matrix protein production and extracellular matrix synthesis. Mechanical stimuli, including fluid shear stress, stretch, compression and cell swelling and decreased mechanical conditions (such as simulated microgravity) can alter the membrane potential and regulate the metabolism of articular chondrocytes via transmembrane ion channel-induced ionic fluxes. This process includes Ca 2+ influx and the resulting mobilization of Ca 2+ that is due to massive released Ca 2+ from stores, intracellular cation efflux and extracellular cation influx. This review brings together published information on mechanosensitive ion channels, such as stretch-activated channels (SACs), voltage-gated Ca 2+ channels (VGCCs), large conductance Ca 2+ -activated K + channels (BK Ca channels), Ca 2+ -activated K + channels (SK Ca channels), voltage-activated H + channels (VAHCs), acid sensing ion channels (ASICs), transient receptor potential (TRP) family channels, and piezo1/2 channels. Data based on epithelial sodium channels (ENaCs), purinergic receptors and N-methyl-d-aspartate (NMDA) receptors are also included. These channels mediate mechanoelectrical physiological processes essential for converting physical force signals into biological signals. The primary channel-mediated effects and signaling pathways regulated by these mechanosensitive ion channels can influence the progression of osteoarthritis during the mechanosensory and mechanoadaptive process of articular chondrocytes.

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Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model

Cited by 56 publications

References 28 publications

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model

The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

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