title: Dietary phosphorus overload aggravates the phenotype of the dystrophin-deficient mdx mouse.
abstract: Duchenne muscular dystrophy is a lethal X-linked disease with no effective treatment. Progressive muscle degeneration, increased macrophage infiltration, and ectopic calcification are characteristic features of the mdx mouse, a murine model of Duchenne muscular dystrophy. Because dietary phosphorus/phosphate consumption is increasing and adverse effects of phosphate overloading have been reported in several disease conditions, we examined the effects of dietary phosphorus intake in mdx mice phenotypes. On weaning, control and mdx mice were fed diets containing 0.7, 1.0, or 2.0 g phosphorus per 100 g until they were 90 days old. Dystrophic phenotypes were evaluated in cryosections of quadriceps and tibialis anterior muscles, and maximal forces and voluntary activity were measured. Ectopic calcification was analyzed by electron microscopy to determine the cells initially responsible for calcium deposition in skeletal muscle. Dietary phosphorus overload dramatically exacerbated the dystrophic phenotypes of mdx mice by increasing inflammation associated with infiltration of M1 macrophages. In contrast, minimal muscle necrosis and inflammation were observed in exercised mdx mice fed a low-phosphorus diet, suggesting potential beneficial therapeutic effects of lowering dietary phosphorus intake on disease progression. To our knowledge, this is the first report showing that dietary phosphorus intake directly affects muscle pathological characteristics of mdx mice. Dietary phosphorus overloading promoted dystrophic disease progression in mdx mice, whereas restricting dietary phosphorus intake improved muscle pathological characteristics and function.
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Wada
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Mizuko
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nagata
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiozuka
authors.affiliation: Kobayashi Institute of Physical Research, Tokyo, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Date
authors.affiliation: Hitachi Aloka Medical, Ltd., Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.affiliation: Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan. Electronic address: cmatsuda@mail.ecc.u-tokyo.ac.jp.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016189:Dystrophin / Q000235:genetics; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D016226:Phosphorus, Dietary / Q000008:administration & dosage*
chemical_list: D016189:Dystrophin; D016226:Phosphorus, Dietary; D002118:Calcium