Ectopic calcification is caused by elevated levels of serum inorganic phosphate in mdx mice.
Ectopic calcification occurs in the skeletal muscle of mdx mice, a dystrophin-deficient animal model of Duchenne muscular dystrophy. The purpose of this study was to clarify the mechanism of the calcification. The calcified deposits were identified as hydroxyapatite, a crystallized form of calcium phosphate, and the serum inorganic phosphate (Pi) level in the mdx mice was approximately 1.4 times higher than that in the normal B10 mice, suggesting that Pi plays a critical role in the ectopic calcification. When C2C12 mouse myoblasts were cultured under high-Pi conditions, myogenic differentiation was retarded while the expression of osteogenic markers such as osteocalcin and Runx2 were upregulated. This was followed by the generation of calcium deposition. Moreover, ectopic calcification reduced to an undetectable level in most of the mdx mice fed a Pi-reduced diet. We therefore conclude that the Pi-induced osteogenesis of muscle cells is responsible for ectopic calcification in the skeletal muscle of mdx mice.
Kikkawa
Namiko
N
Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Ohno
Tomohisa
T
Nagata
Yosuke
Y
Shiozuka
Masataka
M
Kogure
Toshihiro
T
Matsuda
Ryoichi
R
D000818:Animals; D002114:Calcinosis / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006882:Hydroxyapatites / Q000097:blood* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009999:Ossification, Heterotopic / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D010710:Phosphates / Q000097:blood* / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D006882:Hydroxyapatites; D010710:Phosphates; C493716:Runx2 protein, mouse; D015675:Osteocalcin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23