Remifentanil repairs cartilage damage and reduces the degradation of cartilage matrix in post-traumatic osteoarthritis, and inhibits IL-1β-induced apoptosis of articular chondrocytes via inhibition of PI3K/AKT/NF-κB phosphorylation

Abstract

Background: Remifentanil (RFT) is an opioid analgesic with a unique pharmacokinetic profile, and plays an important role in the intra-and post-operative periods. Post-traumatic osteoarthritis (PTO) is a particular type of osteoarthritis (OA) that occurs secondary to a traumatic injury. In the present study, we investigated the effects of RFT both in vivo and in vitro.Methods: In vivo, 50 Sprague Dawley (SD) rats (7 weeks old) were randomly divided into five groups.Four groups of rats received RFT (0.2, 0.5, and 1 μg) or vehicle (PTO group), while the remaining group served as the control. A PTO model in rats was established using the Hulth method. The cartilage damage, articular cartilage formation, and the degradation of cartilage matrix were evaluated. The effects of RFT on cell proliferation, apoptosis, and nuclear factor (NF)-κB phosphorylation were also examined. Results:The results indicated that RFT improved cartilage damage, enhanced articular cartilage formation, and inhibited the degradation of cartilage matrix in PTO model rats. Compared with the control group, the protein levels of Osterix (OSX), Collagen type I alpha 1 (COL1A1), and osteocalcin (OC) were down-regulated in PTO model rats. RFT also inhibited the interleukin-1β (IL-1β)-induced apoptosis of chondrocytes in vitro. Furthermore, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/NF-κB pathway was inhibited both in vitro and in vitro.Conclusions: RFT has significant potential as a therapeutic intervention to ameliorate PTO and provides a foundation for further clinical studies.

WITHDRAWN: Remifentanil preconditioning alleviates myocardial ischemia/reperfusion injury in rats via activating Jagged-1/Notch signaling pathway

“…You are encouraged to use the Version of Record that, when published, will replace this version. The most up-to-date-version is available at https://doi.org/10.1042/BSR20210534 Nowadays, remifentanil is frequently used as an ultra-short acting opioid analgesic in surgical anesthesia due to its unique pharmacokinetic characteristics [20,21].…”

Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology

“…TNF-α can inhibit the synthesis of matrix macromolecules; stimulate the synthesis and secretion of cartilage degrading enzymes, prostaglandin (PGE2); and promote the synthesis of inflammatory factors, leading to cartilage destruction, increased inflammation, and finally degeneration of KOA cartilage [ 60 , 61 ]. Moreover, the activation of PI3K/AKT signaling pathway can inhibit chondrocyte apoptosis and promote the proliferation of chondrocytes to slow down the process of KOA cartilage degeneration [ 62 , 63 ]. Meanwhile, the effective active components in XHLP have the characteristics of inhibiting chondrocyte apoptosis, reducing cartilage matrix catabolism, and eliminating the production of pro-inflammatory cytokines.…”

Remifentanil pretreatment ameliorates H/R-induced cardiac microvascular endothelial cell dysfunction by regulating the PI3K/Akt/HIF-1α signaling pathway

“…According to a previous study, REM can repair post-traumatic osteoarthritis cartilage damage by inhibiting PI3K/Akt/NF-κB phosphorylation, reducing cartilage matrix degradation and inhibiting IL-1β-induced apoptosis of articular chondrocytes [ 39 ]. Mice preconditioned with REM have been reported to display a much lower risk of myocardial injury following I/R procedures, whereas hyperglycemia-induced oxidative stress could diminish REM cardioprotection by damaging the Caveolin-3-regulated PI3K/Akt and JAK2/Stat3 signaling pathways [ 14 ].…”