scholarly journals The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells

2021 ◽  
Vol Volume 14 ◽  
pp. 3959-3967
Author(s):  
Mansour Haddad
2021 ◽  
Vol 28 (4) ◽  
pp. 457-470
Author(s):  
Mansour Haddad

Cannabinoids are abundant signaling compounds; their influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors, CB1 and CB2. One suggested theory is that cannabinoids regulate a variety of physiological processes within the cells of skeletal muscle. Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially significant pathway which plays a role in the control of skeletal muscular activities. The part played by CB1 receptor activation or inhibition with respect to these functions and relevant to targets in the periphery, especially skeletal muscle, is not fully delineated. Thus, the aim of the current research was to explore the influence of CB1 receptor stimulation and inhibition on downstream signaling of the nuclear receptor, NR4A, which regulates the immediate impacts of arachidonyl-2’-chloroethylamide (ACEA) and/or rimonabant in the cells of skeletal muscle. Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling pathways which contribute to alterations in the CB1 receptor. Skeletal muscle cells have often been used; it is well-documented that they express cannabinoid receptors. Quantitative real-time probe-based polymerase chain reaction (qRT-PCR) assays are deployed in order to assess the gene expression characteristics of CB1 receptor signaling. In the current work, it is demonstrated that skeletal muscle cells exhibit functional expression of CB1 receptors. This can be deduced from the qRT-PCR assays; triggering CB1 receptors amplifies both NR4A1 and NR4A3 mRNA gene expression. The impact of ACEA is inhibited by the selective CB1 receptor antagonist, rimonabant. The present research demonstrated that 10 nM of ACEA notably amplified mRNA gene expression of NR4A1 and NR4A3; this effect was suppressed by the addition of 100 nM rimonabant. Furthermore, the CB1 receptor antagonist led to the downregulation of mRNA gene expression of NR4A1, NR4A2 and NR4A3. In conclusion, in skeletal muscle, CB1 receptors were recognized to be important moderators of NR4A1 and NR4A3 mRNA gene expression; these actions may have possible clinical benefits. Thus, in skeletal muscle cells, a possible physiological expression of CB1 receptors was identified. It is as yet unknown whether these CB1 receptors contribute to pathways underlying skeletal muscle biological function and disease processes. Further research is required to fully delineate their role(s).


2019 ◽  
Author(s):  
Rowan P. Rimington ◽  
Darren J. Player ◽  
Neil R.W. Martin ◽  
Mark P. Lewis

AbstractObjectiveOsteoarthritis (OA) is a musculoskeletal disease which contributes to severe morbidity. The monosodium iodoacetate (MIA) rodent model of OA is now well established, however the effect of MIA on surrounding tissues post injection has not been investigated and as such the impact on phenotypic development is unknown. The aim of this investigation was to examine the impact of MIA incubation on skeletal muscle cells in vitro, to provide an indication as to the potential influence of MIA administration of skeletal muscle in vivo.MethodsC2C12 skeletal muscle myotubes were treated with either 4.8μM MIA or 10μM Dexamethasone (DEX, positive atrophic control) up to 72hrs post differentiation and sampled for morphological and mRNA analyses.ResultsSignificant morphological effects (fusion index, number of myotubes and myotube width, p<0.05) were evident, demonstrating a hypertrophic phenotype in control (CON) compared to a hyperplasic phenotype in MIA and DEX. Increases in MAFbx mRNA were also evident between conditions, with post-hoc analysis demonstrating significance between CON and DEX (p<0.001), but not between CON and MIA (p>0.05).ConclusionsThese data indicate a significant impact of both DEX and MIA on regeneration and hypertrophy in vitro and suggest differential activating mechanisms. Future investigations should determine whether skeletal muscle regeneration and hypertrophy is affected in the in vivo rodent model and the potential impact this has on the OA phenotypic outcome.


Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
II Ezeigbo ◽  
C Wheeler-Jones ◽  
S Gibbons ◽  
ME Cleasby

2018 ◽  
Author(s):  
S Höckele ◽  
P Huypens ◽  
C Hoffmann ◽  
T Jeske ◽  
M Hastreiter ◽  
...  

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