Anti–Receptor Activator of Nuclear Factor-κB Ligand Improves Muscle Dysfunction and Strengthens Bone in Laminin-α2–Deficient dy2J/dy2J Dystrophic Mice
Abstract
Congenital muscular dystrophy type 1A (CMD1A) is a severe genetic neuromuscular disorder caused by mutations in the LAMA2 gene, which encodes the laminin α2 subunit, an essential structural protein for maintaining muscle integrity during contraction. Affected children experience progressive muscle damage, hypotonia, delayed motor development and respiratory insufficiency. CMD1A muscles undergo repeated cycles of degeneration and regeneration accompanied by chronic inflammation. Beyond its established role in bone remodeling, the RANK/RANKL/OPG signaling axis has also been implicated in muscle pathophysiology. A 10-day treatment with full-length OPG (FL-OPG- Fc) was previously shown to restore muscle function in a Duchenne muscular dystrophy (DMD) mouse model. In this study, anti-RANKL therapy was evaluated in a more severe mouse model, specifically 4-week-old male dy 2J /dy 2J mice which recapitulate key CMD1A features. A one-month anti-RANKL treatment significantly improved specific muscle strength, increased myofiber cross-sectional area, and reduced edema and immune cell infiltration. It also enhanced bone strength and microarchitecture. However, absolute muscle force and global motor performance remained unchanged. Overall, anti-RANKL treatment improved muscle intrinsic properties and bone parameters in dy 2J /dy 2J dystrophic mice, but these improvements were insufficient to enhance absolute muscle force or global motor performance.
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BibTeX
@article{bouredji2026antireceptor,
title = {{Anti–Receptor Activator of Nuclear Factor-κB Ligand Improves Muscle Dysfunction and Strengthens Bone in Laminin-α2–Deficient dy2J/dy2J Dystrophic Mice}},
author = {Zineb Bouredji and Anthony Facchin and Dounia Hamoudi and Hideo Yagita and Norbert Laroche and Marthe Rousseau and Anteneh Argaw and Jérôme Frenette},
journal = {American Journal of Pathology},
year = {2026},
month = oct,
doi = {10.1016/j.ajpath.2026.04.011},
url = {https://hal.science/hal-05843431v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Anti–Receptor Activator of Nuclear Factor-κB Ligand Improves Muscle Dysfunction and Strengthens Bone in Laminin-α2–Deficient dy2J/dy2J Dystrophic Mice
AU - Zineb Bouredji
AU - Anthony Facchin
AU - Dounia Hamoudi
AU - Hideo Yagita
AU - Norbert Laroche
AU - Marthe Rousseau
AU - Anteneh Argaw
AU - Jérôme Frenette
PY - 2026
DA - 2026/10/29
JO - American Journal of Pathology
DO - 10.1016/j.ajpath.2026.04.011
UR - https://hal.science/hal-05843431v1
AB - Congenital muscular dystrophy type 1A (CMD1A) is a severe genetic neuromuscular disorder caused by mutations in the LAMA2 gene, which encodes the laminin α2 subunit, an essential structural protein for maintaining muscle integrity during contraction. Affected children experience progressive muscle damage, hypotonia, delayed motor development and respiratory insufficiency. CMD1A muscles undergo repeated cycles of degeneration and regeneration accompanied by chronic inflammation. Beyond its established role in bone remodeling, the RANK/RANKL/OPG signaling axis has also been implicated in muscle pathophysiology. A 10-day treatment with full-length OPG (FL-OPG- Fc) was previously shown to restore muscle function in a Duchenne muscular dystrophy (DMD) mouse model. In this study, anti-RANKL therapy was evaluated in a more severe mouse model, specifically 4-week-old male dy 2J /dy 2J mice which recapitulate key CMD1A features. A one-month anti-RANKL treatment significantly improved specific muscle strength, increased myofiber cross-sectional area, and reduced edema and immune cell infiltration. It also enhanced bone strength and microarchitecture. However, absolute muscle force and global motor performance remained unchanged. Overall, anti-RANKL treatment improved muscle intrinsic properties and bone parameters in dy 2J /dy 2J dystrophic mice, but these improvements were insufficient to enhance absolute muscle force or global motor performance.
SN - 0002-9440
SN - 1525-2191
ER -