Ropivacaine relieves pain and prevents chondrocyte degradation probably through Calcineurin/NFAT1 signaling pathway in osteoarthritis rats

Yamamura

et al. 2020

Cells

An improved understanding of fundamental physiological principles and progressive pathophysiological processes in human articular joints (e.g., shoulders, knees, elbows) requires detailed investigations of two principal cell types: synovial fibroblasts and chondrocytes. Our studies, done in the past 8–10 years, have used electrophysiological, Ca2+ imaging, single molecule monitoring, immunocytochemical, and molecular methods to investigate regulation of the resting membrane potential (ER) and intracellular Ca2+ levels in human chondrocytes maintained in 2-D culture. Insights from these published papers are as follows: (1) Chondrocyte preparations express a number of different ion channels that can regulate their ER. (2) Understanding the basis for ER requires knowledge of (a) the presence or absence of ligand (ATP/histamine) stimulation and (b) the extraordinary ionic composition and ionic strength of synovial fluid. (3) In our chondrocyte preparations, at least two types of Ca2+-activated K+ channels are expressed and can significantly hyperpolarize ER. (4) Accounting for changes in ER can provide insights into the functional roles of the ligand-dependent Ca2+ influx through store-operated Ca2+ channels. Some of the findings are illustrated in this review. Our summary diagram suggests that, in chondrocytes, the K+ and Ca2+ channels are linked in a positive feedback loop that can augment Ca2+ influx and therefore regulate lubricant and cytokine secretion and gene transcription.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

K+ and Ca2+ Channels Regulate Ca2+ Signaling in Chondrocytes: An Illustrated Review

Yamamura

et al. 2020

Cells

“…This may be due to drug interactions that lead to modulation via different signaling pathways. Sufentanil may provide protection from myocardial ischemia via the PI3K/Akt-GSK-3β pathway by modulating antiapoptotic proteins (26), and ropivacaine may be a potential treatment for OA by down-regulating the calcineurin/NFAT1 signaling pathway (27). However, the specific mechanism of action of these drugs need to be explored in a future study.…”

Section: Discussionmentioning

confidence: 99%

By regulating miR-182-5p/<i>BCL10</i>/<i>CYCS</i>, sufentanil reduces the apoptosis of umbilical cord mesenchymal stem cells caused by ropivacaine

Sun

Zhang

et al. 2019

BST

Sufentanil is a type of opioid analgesic and is usually used to facilitate painless labor in combination with the local anesthetic ropivacaine. One aim of the current study was to investigate the effects of sufentanil and ropivacaine on umbilical cord mesenchymal stem cells (UCMSCs). A second aim of this study was to determine whether sufentanil attenuated the cytotoxicity of ropivacaine in vitro. UCMSCs were divided into 3 groups: one was treated with ropivacaine at a concentration of 50, 100, 200, or 400 μg/mL, another was treated with sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L, and a third was treated with a combination of ropivacaine at a concentration of 200 μg/mL and sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L. Results indicated that cell proliferation decreased in cells treated with ropivacaine while it increased in cells treated with sufentanil. In addition, sufentanil limited the inhibitory effect of ropivacaine on UCMSC growth in a dose-and time-dependent manner. Combined treatment with ropivacaine at a concentration of 200 μg/mL and sufentanil at a concentration of 500 nmol/L decreased the proportion of dead and apoptotic UCMSCs, and fewer cells were arrested in the S phase compared to cells treated with ropivacaine. Sufentanil inhibited the apoptosis induced by ropivacaine by increasing miR-182-5p, which regulated the expression of mRNA of the pro-apoptotic genes B-cell lymphoma/leukemia 10 (BCL10) and cytochrome c, somatic (CYCS). Sufentanil also increased the expression of mRNA of anti-apoptotic genes. In short, ropivacaine inhibits the cell viability and induces the apoptosis of UCMSCs in vitro while sufentanil attenuates this apoptosis by regulating miR-182-5p/BCL10/CYCS.

“…They maintain healthy articular joints, e.g., by synthesizing and secreting the extracellular matrix and lubricants like hyaluronan and lubricin [ 23 ]. However, they are also involved in developing rheumatoid- and osteoarthritis [ 24 , 25 , 26 , 27 , 28 , 29 ]. Both forms of arthritis are characterized by degeneration and loss of articular cartilage.…”

Section: Introductionmentioning

confidence: 99%

Retrograde Analysis of Calcium Signaling by CaMPARI2 Shows Cytosolic Calcium in Chondrocytes Is Unaffected by Parabolic Flights

et al. 2022

Calcium (Ca2+) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca2+ signaling with a high spatiotemporal resolution is a key challenge. However, particularly on microgravity platforms, experiment time is limited, allowing only a small number of replicates. Furthermore, experiment hardware is exposed to changes in gravity levels, causing experimental artifacts unless appropriately controlled. We introduce a new experimental setup based on the fluorescent Ca2+ reporter CaMPARI2, onboard LED arrays, and subsequent microscopic analysis on the ground. This setup allows for higher throughput and accuracy due to its retrograde nature. The excellent performance of CaMPARI2 was demonstrated with human chondrocytes during the 75th ESA parabolic flight campaign. CaMPARI2 revealed a strong Ca2+ response triggered by histamine but was not affected by the alternating gravitational load of a parabolic flight.