A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy

Sciorati, Clara; Miglietta, Daniela; Buono, Roberta; Pisa, Viviana; Cattaneo, Dario; Azzoni, Emanuele; Brunelli, Silvia; Clementi, Emilio

doi:10.1016/j.phrs.2011.05.003

Cited by 37 publications

(38 citation statements)

References 49 publications

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“…Our results identify iNOS-derived NO as a key messenger in regulating myogenic precursor cell fate and the inflammatory response in a model of muscle damage/regeneration, thus revealing a novel mechanism of inflammation-dependent muscle healing. This information may be used to finely tune therapies based on NO donation and regulation of inflammation that appear to be effective in healing muscle damage after acute or prolonged injury (44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Requirement of Inducible Nitric Oxide Synthase for Skeletal Muscle Regeneration after Acute Damage

Rigamonti

Touvier

Clementi

et al. 2013

The Journal of Immunology

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107

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Adult skeletal muscle regeneration results from activation, proliferation, and fusion of muscle stem cells, such as myogenic precursor cells. Macrophages are consistently present in regenerating skeletal muscles and participate into the repair process. The signals involved in the cross-talk between various macrophage populations and myogenic precursor cells have been only partially identified. In this study, we show a key role of inducible NO synthase (iNOS), expressed by classically activated macrophages in the healing of skeletal muscle. We found that, after sterile injury, iNOS expression is required for effective regeneration of the tissue, as myogenic precursor cells in the muscle of injured iNOS−/− mice fail to proliferate and differentiate. We also found that iNOS modulates inflammatory cell recruitment: damaged muscles of iNOS−/− animals express significantly higher levels of chemokines such as MIP2, MCP1, MIP-1α, and MCP1, and display more infiltrating neutrophils after injury and a persistence of macrophages at later time points. Finally, we found that iNOS expression in the injured muscle is restricted to infiltrating macrophages. To our knowledge, these data thus provide the first evidence that iNOS expression by infiltrating macrophages contributes to muscle regeneration, revealing a novel mechanism of inflammation-dependent muscle healing.

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Section: Discussionmentioning

confidence: 99%

Requirement of Inducible Nitric Oxide Synthase for Skeletal Muscle Regeneration after Acute Damage

Rigamonti

Touvier

Clementi

et al. 2013

The Journal of Immunology

Self Cite

107

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“…In sgca KO mice, NCX 320 (cyclooxygenaseinhibiting NO donator) treatment for 8 months leads to an increase in the number of newly formed fibers, as well as an increase of the number of MuSCs. Moreover, MuSCs exhibit an increased ability to differentiate in vitro and to express the differentiation markers myogenin and myosin heavy chain, indicative of their good regenerative potential (298). Finally, mdx mice supplemented for 10 weeks with nicotinamide riboside exhibit an increased number of MuSCs while muscle regeneration is improved, indicating that nicotinamide riboside also prevents MuSC senescence in muscular dystrophy (287,361), as it does in aging muscle (see Section X-B-2: In aging) (Fig.…”

Section: A Exercise As Therapymentioning

confidence: 94%

“…It is worth mentioning that the importance of inflammation and inflammatory cells in the establishment and maintenance of the pathology during muscular dystrophies is recognized, whereas the phenotype and functions of these cells have been overlooked. In this context, it is interesting to mention that antioxidant treatment has been shown to reduce the amount of inflammatory cells in these diseases, and this decrease is associated with the improvement observed in the muscle (298).…”

Section: A Exercise As Therapymentioning

confidence: 99%

Redox Control of Skeletal Muscle Regeneration

Moal

Pialoux

Juban

et al. 2017

Antioxidants & Redox Signaling

152

120

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Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

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“…up to the end of the observation period, which was set at 12 months to mimic a chronic treatment in a clinical setting with patients. Several mechanisms synergised to yield the therapeutic effect of the combined therapy: significant reduction in both fibre damage and inflammation and increases in the myogenic precursor cells number and differentiation capacity, which preserve the long-term regeneration capacity of muscle [119][120][121]. Other actions of NO on skeletal muscle such as vasodilation and thus reduction of the ischaemia induced by nNOS displacement, increase in glucose uptake and in energy generation [106] may also have contributed to muscle repair.…”

Section: Nitric Oxide and The Therapy Of Muscular Dystrophiesmentioning

confidence: 99%

Nitric Oxide in Myogenesis and Therapeutic Muscle Repair

Palma

Clementi

2012

Mol Neurobiol

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Nitric oxide is a short-lived intracellular and intercellular messenger. The first realisation that nitric oxide is important in physiology occurred in 1987 when its identity with the endothelium-derived relaxing factor was discovered. Subsequent studies have shown that nitric oxide possesses a number of physiological functions that are essential not only to vascular homeostasis but also to neurotransmission, such as in the processes of learning and memory and endocrine gland regulation, as well as inflammation and immune responses. The discovery in 1995 that a splice variant of the neuronal nitric oxide synthase is localised at the sarcolemma via the dystrophin-glycoprotein complex and of its displacement in Duchenne muscular dystrophy has stimulated a host of studies exploring the role of nitric oxide in skeletal muscle physiology. Recently, nitric oxide has emerged as a relevant messenger also of myogenesis that it regulates at several key steps, especially when the process is stimulated for muscle repair following acute and chronic muscle injuries. Here, we will review briefly the mechanisms and functions of nitric oxide in skeletal muscle and discuss its role in myogenesis, with specific attention to the promising nitric oxide-based approaches now being explored at the pre-clinical and clinical level for the therapy of muscular dystrophy.

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A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy

Abstract: Graphical abstract

Cited by 37 publications

References 49 publications

Requirement of Inducible Nitric Oxide Synthase for Skeletal Muscle Regeneration after Acute Damage

Requirement of Inducible Nitric Oxide Synthase for Skeletal Muscle Regeneration after Acute Damage

Redox Control of Skeletal Muscle Regeneration

Nitric Oxide in Myogenesis and Therapeutic Muscle Repair

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