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Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy

  • Muscle and Bone (L Bonewald and M Hamrick, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In Duchenne muscular dystrophy (DMD), the progressive skeletal and cardiac muscle dysfunction and degeneration is accompanied by low bone mineral density and bone fragility. Glucocorticoids, which remain the standard of care for patients with DMD, increase the risk of developing osteoporosis. The scope of this review emphasizes the mutual cohesion and common signaling pathways between bone and skeletal muscle in DMD.

Recent Findings

The muscle-bone interactions involve bone-derived osteokines, muscle-derived myokines, and dual-origin cytokines that trigger common signaling pathways leading to fibrosis, inflammation, or protein synthesis/degradation. In particular, the triad RANK/RANKL/OPG including receptor activator of NF-kB (RANK), its ligand (RANKL), along with osteoprotegerin (OPG), regulates bone matrix modeling and remodeling pathways and contributes to muscle pathophysiology in DMD.

Summary

This review discusses the importance of the muscle-bone unit in DMD and covers recent research aimed at determining the muscle-bone interactions that may eventually lead to the development of multifunctional and effective drugs for treating muscle and bone disorders regardless of the underlying genetic mutations in DMD.

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Abbreviations

ActRIIA:

activin IIA receptor

ActRIIB-Fc:

soluble myostatin decoy receptor

AR:

androgen receptor

BMD:

bone mineral density

CK:

creatine kinase

DMD:

Duchenne muscular dystrophy

EDL:

extensor digitorum longus

FGF-23:

fibroblast growth factor 23

FL-OPG-Fc:

full-length osteoprotegerin linked to a Fc fragment

GC (s):

glucocorticoid (s)

IGF-1:

insulin growth factor 1

IL-1:

interleukin-1

IL-6:

interleukin-6

IL-6R:

interleukin-6 receptor

IL-10:

interleukin-10

IL-10 −/− mdx :

ablation of IL-10 expression in mdx mice

IL-15:

interleukin-15

IL-17:

interleukin-17

MSCs:

mesenchymal stem cells

NO:

nitric oxide

NO-cGMP:

nitric oxide-cyclic guanosine monophosphate

OPG:

osteoprotegerin

OPN:

osteopontin

PDE-5:

phosphodiesterase type 5

RANK:

receptor activator of NF-κB

RANKL:

receptor activator of NF-κB ligand

SERCA:

sarco(endo)plasmic reticulum Ca2+-ATPase

Sol:

soleus

TGF-β:

transforming growth factor β

TNF-α:

tumor necrosis factor α

TRAF:

TNF receptor-associated factor

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

VBP15:

vamorolone

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Funding

This work was supported by the Ryan’s Quest foundation, Jesse’s Journey, and Natural Sciences and Engineering Research Council of Canada (NSERC).

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Authors and Affiliations

  1. Centre Hospitalier Universitaire de Québec, Centre de Recherche du Centre Hospitalier de l’Université Laval (CHUQ-CHUL), Axe Neurosciences, Université Laval, Quebec City, QC, G1V 4G2, Canada

    Antoine Boulanger Piette, Dounia Hamoudi, Laetitia Marcadet, Françoise Morin, Anteneh Argaw & Jérôme Frenette

  2. Division of Endocrinology and Metabolism, Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON, K1H 8L1, Canada

    Leanne Ward

  3. Département de Réadaptation, Faculté de Médecine, Université Laval, Quebec City, QC, G1V 0A6, Canada

    Jérôme Frenette

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  1. Antoine Boulanger Piette
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  2. Dounia Hamoudi
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  3. Laetitia Marcadet
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  4. Françoise Morin
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  5. Anteneh Argaw
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  6. Leanne Ward
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  7. Jérôme Frenette
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Correspondence to Jérôme Frenette.

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Conflict of Interest

Leanne Ward reports participating in clinical trials with AMGEN.

Jérôme Frenette has a patent issued (20180064810).

Laetitia Marcadet, Anteneh Argaw, Antoine Boulanger, Françoise Morin Piette, and Dounia Hamoudi declare no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Boulanger Piette, A., Hamoudi, D., Marcadet, L. et al. Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy. Curr Osteoporos Rep 16, 541–553 (2018). https://doi.org/10.1007/s11914-018-0468-2

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