title: Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.
abstract: Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy.
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Kuraoka
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: En
authors.initials: E
authors.lastname: Kimura
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Mental Health Policy and Evaluation, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hisateru
authors.initials: H
authors.lastname: Tachimori
authors.affiliation: Department of Psychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yonemoto
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. Electronic address: takeda@ncnp.go.jp.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D003964:Diaphragm / Q000378:metabolism; D004285:Dogs; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000503:physiopathology*; D053495:Osteopontin / Q000378:metabolism*; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004179:Cobra Cardiotoxin Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D053495:Osteopontin; D020780:Matrix Metalloproteinase 9