Cannabinoid type 2 receptor manipulates skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization in IR injury in mice

Jiang, Penghao; Wang, Linlin; Zhang, Mengzhou; Zhang, Miao; Wang, Changliang; Zhao, Rui; Guan, Dawei

doi:10.1016/j.lfs.2020.117989

Cited by 15 publications

(16 citation statements)

References 39 publications

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“…Similar to CB 1 , also CB 2 expression tended to be increased upon RT. Pharmaceutical CB 2 agonism increased the expression of satellite cell growth markers such as MyoD and myogenin 23 , while CB 2 knock-out decreased MyoD and myogenin expression during murine muscle regeneration 13 . Therefore, the increased CB 2 expression in the present study might reflect an improved myogenic capacity, e.g.…”

Section: Discussionmentioning

confidence: 95%

“…inflammation 8 , 9 , malnutrition 10 , metabolic dysregulations 11 and physical inactivity 12 . Recently, there is a growing interest in the role of the cannabinoid system in controlling plasticity in metabolic tissues, such as adipose tissue and skeletal muscle 13 – 15 . For example, increased endocannabinoid activity (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas the signaling responses upon CB binding are well described in neural tissues, it is not understood how CB 1/2 affect (MAPK-mediated) downstream signaling in skeletal muscle tissue. Nevertheless, recent developments in mice indicate that CB signaling interferes with muscle metabolism 19 , muscle maintenance 15 and regenerative processes 13 . CB 1 antagonism in mice reversed age-related metabolic dysregulations 19,20 and improved muscle regeneration in a murine model of Duchenne muscular dystrophy 14 .…”

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confidence: 99%

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Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Dalle

Koppo

2021

Sci Rep

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Aged skeletal muscle undergoes metabolic and structural alterations eventually resulting in a loss of muscle strength and mass, i.e. age-related sarcopenia. Therefore, novel targets for muscle growth purposes in elderly are needed. Here, we explored the role of the cannabinoid system in muscle plasticity through the expression of muscle cannabinoid receptors (CBs) in young and old humans. The CB1 expression was higher (+ 25%; p = 0.04) in muscle of old (≥ 65 years) vs. young adults (20–27 years), whereas CB2 was not differently expressed. Furthermore, resistance exercise tended to increase the CB1 (+ 11%; p = 0.055) and CB2 (+ 37%; p = 0.066) expression in muscle of older adults. Interestingly, increases in the expression of CB2 following resistance exercise positively correlated with changes in key mechanisms of muscle homeostasis, such as catabolism (FOXO3a) and regenerative capacity (Pax7, MyoD). This study for the first time shows that CB1 is differentially expressed with aging and that changes in CB2 expression upon resistance exercise training correlate with changes in mediators that play a central role in muscle plasticity. These data confirm earlier work in cells and mice showing that the cannabinoid system might orchestrate muscle growth, which is an incentive to further explore CB-based strategies that might counteract sarcopenia.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Dalle

Koppo

2021

Sci Rep

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“…The mechanistic role of CB 2 was further evaluated with pharmacological and genetic (ant)agonistic approaches. CB 2 knockout impaired the regeneration upon muscle reperfusion‐ischemia in mice (Jiang et al, 2020; M. Zhang et al, 2019). Knockout resulted in more severe myofiber necrosis, a lower number of newly formed myofibers with central nuclei, a smaller average myofiber cross‐sectional area, decreased expression of MyoD and myogenin, increased fibrosis, more inflammatory cell infiltration, and a shift in macrophage polarization toward a pro‐inflammatory phenotype (Jiang et al, 2020).…”

Section: Cannabinoid System and Muscle Homeostasis: Paths And Challengesmentioning

confidence: 99%

Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity

Dalle

Schouten

Meeus

et al. 2022

Journal Cellular Physiology

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The cannabinoid system is ubiquitously present and is classically considered to engage in neural and immunity processes. Yet, the role of the cannabinoid system in the whole body and tissue metabolism via central and peripheral mechanisms is increasingly recognized. The present review provides insights in (i) how cannabinoid signaling is regulated via receptor-independent and -dependent mechanisms and (ii) how these signaling cascades (might) affect skeletal muscle plasticity and physiology.Receptor-independent mechanisms include endocannabinoid metabolism to eicosanoids and the regulation of ion channels. Alternatively, endocannabinoids can act as ligands for different classic (cannabinoid receptor 1 [CB 1 ], CB 2 ) and/or alternative (e.g., TRPV1, GPR55) cannabinoid receptors with a unique affinity, specificity, and intracellular signaling cascade (often tissue-specific). Antagonism of CB 1 might hold clues to improve oxidative (mitochondrial) metabolism, insulin sensitivity, satellite cell growth, and muscle anabolism, whereas CB 2 agonism might be a promising way to stimulate muscle metabolism and muscle cell growth. Besides, CB 2 ameliorates muscle regeneration via macrophage polarization toward an anti-inflammatory phenotype, induction of MyoD and myogenin expression and antifibrotic mechanisms. Also TRPV1 and GPR55 contribute to the regulation of muscle growth and metabolism. Future studies should reveal how the cannabinoid system can be targeted to improve muscle quantity and/or quality in conditions such as ageing, disease, disuse, and metabolic dysregulation, taking into account challenges that are inherent to modulation of the cannabinoid system, such as central and peripheral side effects.

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“…It further regulates the expression of β-isoform myosin heavy chain to decrease contractile velocity under pressure overload in hearts [45]. CB2 also mitigates myocardial injury via manipulating macrophage polarization to maintain M1/M2 macrophage balance [46]. Due to the additional localization in fibroblast, CB2 also directly regulates the myofibroblast activation and thereby defending unwelcome myocardial fibrosis [30].…”

Section: Cardiac Fibrosismentioning

confidence: 99%

Cannabinoid Receptors in Myocardial Injury: A Brother Born to Rival

Tang

Zheng

et al. 2021

IJMS

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Cannabinoid receptors typically include type 1 (CB1) and type 2 (CB2), and they have attracted extensive attention in the central nervous system (CNS) and immune system. Due to more in-depth studies in recent years, it has been found that the typical CB1 and CB2 receptors confer functional importance far beyond the CNS and immune system. In particular, many works have reported the critical involvement of the CB1 and CB2 receptors in myocardial injuries. Both pharmacological and genetic approaches have been used for studying CB1 and CB2 functions in these studies, revealing that the brother receptors have many basic differences and sometimes antagonistic functions in a variety of myocardial injuries, despite some sequence or location identity they share. Herein, we introduce the general differences of CB1 and CB2 cannabinoid receptors, and summarize the functional rivalries between the two brother receptors in the setting of myocardial injuries. We point out the importance of individual receptor-based modulation, instead of dual receptor modulators, when treating myocardial injuries.

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Cannabinoid type 2 receptor manipulates skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization in IR injury in mice

Cited by 15 publications

References 39 publications

Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity

Cannabinoid Receptors in Myocardial Injury: A Brother Born to Rival

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