Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice

Cell Structure and Function

Toshihiro Kogure¹  Yosuke Nagata²  Namiko Kikkawa²  Ryoichi Matsuda²  Masataka Shiozuka²  Tomohisa Ohno² 

[1] Department of Earth and Planetary Science, Graduate School of Science, The University of Tokyo;Graduate School of Arts and Sciences, The University of Tokyo

关键词: ectopic calcification;    inorganic phosphate;    mdx mouse;    muscular dystrophy;    skeletal muscle;   

DOI  :  10.1247/csf.08039

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(49)Cited-By(10)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.

【 授权许可】

Unknown