Dose-dependent cannabidiol-induced elevation of intracellular calcium and apoptosis in human articular chondrocytes.

Dose-dependent cannabidiol-induced elevation of intracellular calcium and apoptosis in human articular chondrocytes.

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Dose-dependent cannabidiol-induced elevation of intracellular calcium and apoptosis in human articular chondrocytes.

J Orthop Res. 2019 Aug 05;:

Authors: Winklmayr M, Gaisberger M, Kittl M, Fuchs J, Ritter M, Jakab M

Abstract
Cannabidiol (CBD) is the most abundant non-psychoactive compound of Cannabis sativa extracts. Cannabinoids have been shown to exhibit anti-inflammatory, analgesic, antioxidant, neuroprotective and anti-tumorigenic effects. In the present study we investigated the effects of CBD on human articular chondrocytes. Cell viability was determined by Resazurin assays. Apoptosis was analyzed by Annexin-V/7-AAD staining followed by flow cytometry. Caspase 3/7 activity was measured with caspase assays. Intracellular Ca2+ ([Ca2+ ]i ) was monitored by time-lapse fluorescence imaging. The perforated whole-cell patch clamp technique was used for measuring the cell membrane potential. Erk1/2 phosphorylation was assessed by Western blot analysis. The chondrocyte cell line C28/I2 and primary chondrocytes showed a reduced viability after treatment with concentrations of CBD greater than 4 µM. This apoptotic effect was accompanied by an increase of caspase 3/7 activity and an increase in the early apoptotic cell population. CBD elevated [Ca2+ ]i , which was accompanied by a depolarization of the cell membrane potential. The increase of [Ca2+ ]i was abrogated, when Ca2+ was omitted from the bath solution, indicating an influx of extracellular Ca2+ . The cannabinoid receptor 1 (CB1) antagonist AM251 inhibited the Ca2+ influx triggered by CBD. Preincubation with AM251 reduced the toxic effects of CBD. By looking for mediators of the apoptotic CBD effect downstream of the CB1 receptor, enhanced Erk1/2 phosphorylation could be detected after CBD treatment. However, this Erk1/2 activation proved to be unaffected by CB1 receptor blockage. The present study demonstrates, that CBD promotes apoptosis and [Ca2+ ]i elevation in human articular chondrocytes via a CB1-receptor-mediated mechanism. This article is protected by copyright. All rights reserved.

PMID: 31378964 [PubMed – as supplied by publisher]


https://www.ncbi.nlm.nih.gov/pubmed/31378964?dopt=Abstract

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1jYCQzi_o_qLYr-oQfnMhShgOXkvGma3vcnBGJtrBhuJMOvEVJ

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