ReferenceID 2555
Oxoglaucine mediates Ca2+ influx and activates autophagy to alleviate osteoarthritis through the TRPV5/calmodulin/CAMK-II pathway
Br J Pharmacol
BACKGROUND AND PURPOSE: Stimulation of calcium influx and suppression of autophagy play important roles in the pathogenesis of osteoarthritis (OA). In this study, we used a novel inhibitor of TRPV5 cation channels - oxog
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Record Fields
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- Reference Id
- 2555
- Evidence Id
- 19145
- Core Evidence Id
- 19145
- Source Reference Id
- 5116
- Herb2 Reference Id
- HBREF005913
- Subject Paper Key
- HBIN038452_33786819
- Pubmed Id
- 33786819
- Doi
- 10.1111/bph.15466
- Paper Title
- Oxoglaucine mediates Ca2+ influx and activates autophagy to alleviate osteoarthritis through the TRPV5/calmodulin/CAMK-II pathway
- Paper Abstract
- BACKGROUND AND PURPOSE: Stimulation of calcium influx and suppression of autophagy play important roles in the pathogenesis of osteoarthritis (OA). In this study, we used a novel inhibitor of TRPV5 cation channels - oxoglaucine to attenuate progression of deterioration and pathological changes in OA patient-derived chondrocytes and OA animal model, by activating autophagy. EXPERIMENTAL APPROACH: Inhibition by oxoglaucine of calcium influx was assessed in cells.. Analyses were also carried out to investigate the effect of oxoglaucine on OA by detection of anti-inflammatory response, TRPV5/CAMK-II/calmodulin pathway, autophagy, and cartilage protection both in vitro and in vivo. demonstrated by macroscopic evaluation and histological findings. KEY RESULTS: Oxoglaucine suppressed expression of proinflammatory and apoptosis-related proteins, including TNF-alpha, IL-6, IL-1beta, MMP-13, CASP-3, and BAX, and prevented matrix degradation in OA chondrocytes. It also successfully blocked Ca2+ influx, activating autophagy dose-dependently asshown by up-regulated expression of LC-3II/I, Beclin-1, ATG5, ATG7, higher autophagic influx and formation of autophagic vesicles. It also decreased expression of mRNA and protein of TRPV5, CAMK-II, and calmodulin. Conversely, 1,25-dihydroxyvitamin D3, anagonist of TRPV5 channels, reversed the oxoglaucine-induced calcium influx inhibition and autophagy activation, demonstrating the association of oxoglaucine with TRPV5. Further, oxoglaucine prevented the apoptosis and matrix degradation of articular cartilage in a rat model of OA. CONCLUSION AND IMPLICATIONS: Oxoglaucine protects against cartilage damage by blocking the TRPV5/CAMK-II/calmodulin pathway to inhibit Ca2+ influx and activate autophagy. Our results indicate that oxoglaucine has the potential to become a candidate drug for treatment of OA.
- Journal
- Br J Pharmacol
- Publish Year
- 2021
- Experiment Subject
- rat; patient
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Osteoarthritis
- Paper Title Cn
- Paper Title En
- Oxoglaucine mediates Ca2+ influx and activates autophagy to alleviate osteoarthritis through the TRPV5/calmodulin/CAMK-II pathway
- Bilingual Status
- semi_complete