Editorial Inflammation in Muscle Repair, Aging, and...

EditorialInflammation in Muscle Repair, Aging, and Myopathies

Marina Bouché,1 Pura Muñoz-Cánoves,2 Fabio Rossi,3 and Dario Coletti4

1 DAHFMO, Unit of Histology and Medical Embryology, Sapienza University of Rome, Via Antonio Scarpa 14, 00161 Rome, Italy2 Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF),CIBER on Neurodegenerative Diseases (CIBERNED), Institucio Catalana de Recerca i Estudis Avancats (ICREA),Doctor Aiguader 88, 08003 Barcelona, Spain

3The Biomedical Research Centre, UBC, Vancouver, BC, Canada V6T 1Z34B2A Biology of Adaptation and Aging, Pierre and Marie Curie University (Paris 6), 7 quai St Bernard, 75252 Paris Cedex 5, France

Correspondence should be addressed to Marina Bouche; [email protected]

Received 17 July 2014; Accepted 17 July 2014; Published 4 August 2014

Copyright © 2014 Marina Bouche et al.This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Numerous recent studies have expanded our knowledge onthe complexity of the immune system and its contributionto skeletal muscle repair, aging, and myopathies. Indeed, it isbecoming clear that a precisely regulated cross talk betweenmuscle and immune cells, involving endocrine/paracrine andcell-cell contact interactions, is required for muscle repairand maintenance of muscle homeostasis. Alterations of thesemechanisms lead to unsuccessful repair in response to directmechanical trauma (acute injury) or following secondarydamage as a consequence of aging or genetic neuromusculardefects. In fact, though the capacity of muscle to regeneraterelies primarily on a specific population of muscle stem cells,named satellite cells, the inflammatory cells that infiltratethe injured muscle appear to be as critical for successfulregeneration. Conversely, if damage persists, as in chronicmyopathies, inflammatory cell infiltration is perpetuated andleads to progressivemuscle fibrosis, thus exacerbating diseaseseverity.

While the number of scientific publications on the topic ofskeletal muscle inflammation has steadily grown over the lasttwo decades, the notion of inflammation as a common featurein muscle degeneration occurring in aging and myopathiesand its association with altered muscle has to our knowledgenever previously been addressed and discussed in dedicatedjournal issues before.

The main focus of this special issue is to bring togetherstudies that used different experimental approaches in vivo orin vitro to dissect the dynamic changes taking place in specific

immune cell populations, their cross talk with other cell typeswithin the muscle milieu, and their contribution to normalversus pathological muscle repair.

Among the seven review articles, E. Rigamonti et al.discuss the current available literature about the role ofmacrophage populations in tissue injury and repair witha particular focus on skeletal muscle regeneration. Beyondtheir role in innate immunity, macrophages are now recog-nized as crucial players in orchestrating the healing of variousinjured tissues, including skeletal muscle. In this review theauthors discuss the involvement of specific macrophage sub-populations in these processes and the complexity of definingmacrophage subpopulations in vivo, since the in vitro criteriaused to define M1 and M2 macrophages cannot be strictlyapplied to in vivo settings. Indeed, it is still a matter of debatewhether the sequential presence of different macrophagepopulations results from a dynamic shift in macrophagepolarization or from the recruitment of new circulatingmonocytes. Thus, to identify the molecular determinants ofmacrophage polarization is certainly one of the major tasksin developing effective targeted therapies for genetic defectsof the tissue and muscle diseases associated with chronicinflammation.

However, although macrophages are emerging as indis-pensable for damage control and tissue remodeling followingmuscle injury and as principal mediators of pathologicalskeletal remodeling in diseases such as idiopathic inflam-matory myositis (IIMs) and muscular dystrophies (MDs),

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014, Article ID 821950, 3 pageshttp://dx.doi.org/10.1155/2014/821950

2 BioMed Research International

the involvement of other immune cells in promoting orpreventing muscle damage resolution is also emerging. Thecurrent knowledge and recent advances on the involvementof different innate immune cells in MDs and the emerg-ing role of additional cell populations within the acquiredimmune response are being discussed in the review article byL. Madaro and M. Bouche.

It is widely believed that any disruption in the coordi-nated initiation, progression, and resolution of inflammationcan lead to persistent muscle damage and impairment ofregeneration, which in many cases is also characterized bydevelopment of fibrosis, as observed in MDs. Indeed, theprocess of fibrosis, whose underlying mechanisms are notfully elucidated yet, represents one important deleteriousconsequence of impaired muscle repair. In this specialissue, Y. Kharraz et al. discuss new developments in ourunderstanding of the mechanisms leading to fibrosis inDuchenne muscular dystrophy (DMD) and several recentadvances towards reverting it, as well as potential treatmentsto attenuate disease progression.

Although blunting inflammation would not restore theprimary defect in MDs, the emerging consensus is that mul-tiple strategies addressing different aspects of the pathology,which may eventually converge, may be successful. Indeed,various therapies under development are directed towardrescuing the dystrophic muscle damage using gene transferor cell-therapy.

A. Farini et al. discuss current knowledge about involve-ment of immune system responses to experimental therapiesin MDs and how the different components of the immunesystem response are differently activated against cell- or gene-therapy both in a specific manner, linked to the type ofcell or vector used, and according to MDs-specific immune-pathogenetic mechanisms.

In this context, S. M. Maffioletti et al. give an in-depth overview of the main players and issues involved inthe mechanisms and dynamics that impair the efficacy ofcell transplants in DMD and discuss potential approachesthat might be beneficial for future regenerative therapies ofskeletal muscle.

Muscle wasting linked to immune response is not, how-ever, a feature restricted to genetic diseases.

In cancer cachexia, for example, inflammatory cytokinesare important not only to establish tumor-host interactionand deregulate inflammatory response to tumor burden,but also to mediate muscle wasting by directly targetingmuscle tissue. In the review by J. K. Onesti and D. C.Guttridge a summary of the clinical implications, backgroundof inflammatory cytokines, and the origin and sources ofprocachectic factors is provided. Molecular mechanisms andpathways are also described to elucidate the link betweenthe immune response caused by the presence of the tumorand cytokine-dependent inhibition of muscle regeneration,ultimately resulting in muscle wasting.

Muscle wasting is also a feature of IIMs, a wide rangeof autoimmune diseases, characterized clinically by reducedmuscle endurance and weakness, chronic inflammation,and infiltration by immune/inflammatory cells in skeletal

muscles. Treatments for IIMs are based on lifelong immuno-suppressive therapy, which comes with well-known adverseeffects; recovery is incomplete for many patients. More effec-tive therapies, with reduced side effects, are highly desirable.In this context, C. Crescioli proposes vitamin D receptor(VDR) agonists as candidates in future treatment of IIMs. Inher review she summarizes the pleiotropic anti-inflammatoryproperties of VDRs with potentially limited adverse effects.

Similarly, A. Costa et al., in one out of the four originalcontributions in this issue, propose Arg-vasopressin- (AVP-)dependent pathways as an interesting strategy to counteractmuscle decline in aging or myopathies. Indeed, the authorsshow that overexpression of the AVP receptor V1a in skeletalmuscle in vivo increases the expression of regenerative mark-ers,modulates immune response, and attenuates fibrogenesis,thus enhancing muscle regeneration and counteracting thenegative effects of the proinflammatory cytokine TNF.

On the other hand, M. Pelosi et al. addressed the effectsof IL-6, a multifaceted pleiotropic cytokine, on the myogenicprogram. In physiological conditions IL-6 is required formuscle homeostasis, but in several pathological conditionsits level increases and it contributes to muscle wasting. Inthis paper the authors explored the molecular mechanismsunderlying IL-6-dependent inhibition of the myogenic pro-gram and identified potential molecular mediators of theseeffects.

It is well known that the inflammatory response playsan important role also in the development of ischemic heartdisease. In this context, G. D. Duerr et al. demonstrate in thisissue that osteopontin (OPN) has a cardioprotective effect.OPN is a matricellular protein and cytokine involved in theregulation of macrophage function and as a remodeling-associated mediator in different tissues. Using in vivomodelsthey show that lack of OPN prevents heart remodelingin a murine model of ischemic cardiopathy, altering theexpression of contractile elements and chemokines, as well asremodeling factors. These findings may further support thetherapeutical perspective for osteopontin as a possible targetin protection of the ischemic heart.

To conclude this special issue, C. Sciorati et al. charac-terize the ability of the 7-Tesla magnetic resonance imaging(MRI) to reveal specific inflammatory events in the skeletalmuscle using a mouse model of IIM. One of the limits inunderstanding the etiopathogenesis of muscle inflammatorydiseases is the paucity of approaches for the noninvasivestudy of inflamed tissues. The authors provide an in-depthnoninvasive characterization of this myositis model, provingthe efficacy of MRI as an informative and noninvasiveanalytical tool for studying in vivo immune-mediated muscleinvolvement. Indeed, the availability of noninvasive tools tomonitor muscle inflammation will permit reduction in thenumber of animals necessary for experimental studies andwill increase the amount of relevant information that can bederived from single animals followed over time. At the sametime, this imaging modality will complement informationderived from histopathological studies that encompass onlylimited areas of tissue and therefore suffer from potentialsampling bias.

BioMed Research International 3

What emerges from this special issue is thatinflammation-regulated muscle repair in aging and diseaseis an active and rapidly advancing research field, and wehope that the papers here collected will help to connectfundamental science with biomedical research on severemyopathies, with the aim of opening new venues for therapy.It is our wish that these papers will also be a useful tool forthe inflammation and skeletal muscle research communityand that they will attract and motivate investigators fromdifferent scientific areas to this important field of research.

Acknowledgments

We would like to thank the BMRI Editorial Office for theopportunity of producing this special issue and all contribut-ing authors who made this possible. Our sincerest thanksalso go to the outstanding external reviewers for their expertassistance.

Marina BouchePura Munoz-Canoves

Fabio RossiDario Coletti

Submit your manuscripts athttp://www.hindawi.com

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Anatomy Research International

PeptidesInternational Journal of


Hindawi Publishing Corporation http://www.hindawi.com

International Journal of

Volume 2014

Zoology


Molecular Biology International

GenomicsInternational Journal of


The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014


BioinformaticsAdvances in

Marine BiologyJournal of



Signal TransductionJournal of


BioMed Research International

Evolutionary BiologyInternational Journal of



Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Genetics Research International


Advances in

Virolog y

Hindawi Publishing Corporationhttp://www.hindawi.com

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational



Enzyme Research


International Journal of

Microbiology

Editorial Inflammation in Muscle Repair, Aging, and...

Documents

Transcript of Editorial Inflammation in Muscle Repair, Aging, and...