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 p...
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| Veröffentlicht in: | Cell Structure and Function 2009, Vol.34(2), pp.77-88 |
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| creator | Kikkawa, Namiko Ohno, Tomohisa Nagata, Yosuke Shiozuka, Masataka Kogure, Toshihiro Matsuda, Ryoichi |
| description | 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. |
| doi_str_mv | 10.1247/csf.08039 |
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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.</description><identifier>ISSN: 0386-7196</identifier><identifier>EISSN: 1347-3700</identifier><identifier>DOI: 10.1247/csf.08039</identifier><identifier>PMID: 19622873</identifier><language>eng</language><publisher>Japan: Japan Society for Cell Biology</publisher><subject>Animals ; Calcinosis - blood ; Calcinosis - metabolism ; Calcinosis - pathology ; Cell Line ; Core Binding Factor Alpha 1 Subunit - metabolism ; Disease Models, Animal ; ectopic calcification ; Fibroblast Growth Factors - blood ; Hydroxyapatites - blood ; Hydroxyapatites - metabolism ; inorganic phosphate ; mdx mouse ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - ultrastructure ; muscular dystrophy ; Muscular Dystrophy, Duchenne - blood ; Muscular Dystrophy, Duchenne - metabolism ; Muscular Dystrophy, Duchenne - pathology ; Myoblasts - drug effects ; Myoblasts - metabolism ; Myoblasts - pathology ; Ossification, Heterotopic - blood ; Ossification, Heterotopic - metabolism ; Ossification, Heterotopic - pathology ; Osteocalcin - metabolism ; Phosphates - blood ; Phosphates - metabolism ; skeletal muscle</subject><ispartof>Cell Structure and Function, 2009, Vol.34(2), pp.77-88</ispartof><rights>2009 by Japan Society for Cell Biology</rights><rights>Copyright Japan Science and Technology Agency 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-e472f9a0bda5f76e5ec6a62dc4a2aea6bfa8a4584e92a86fa291954498cb02f23</citedby><cites>FETCH-LOGICAL-c607t-e472f9a0bda5f76e5ec6a62dc4a2aea6bfa8a4584e92a86fa291954498cb02f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19622873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kikkawa, Namiko</creatorcontrib><creatorcontrib>Ohno, Tomohisa</creatorcontrib><creatorcontrib>Nagata, Yosuke</creatorcontrib><creatorcontrib>Shiozuka, Masataka</creatorcontrib><creatorcontrib>Kogure, Toshihiro</creatorcontrib><creatorcontrib>Matsuda, Ryoichi</creatorcontrib><title>Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice</title><title>Cell Structure and Function</title><addtitle>Cell Struct. Funct.</addtitle><description>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.</description><subject>Animals</subject><subject>Calcinosis - blood</subject><subject>Calcinosis - metabolism</subject><subject>Calcinosis - pathology</subject><subject>Cell Line</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>Disease Models, Animal</subject><subject>ectopic calcification</subject><subject>Fibroblast Growth Factors - blood</subject><subject>Hydroxyapatites - blood</subject><subject>Hydroxyapatites - metabolism</subject><subject>inorganic phosphate</subject><subject>mdx mouse</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred mdx</subject><subject>Microscopy, Electron, Scanning</subject><subject>Microscopy, Electron, Transmission</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - ultrastructure</subject><subject>muscular dystrophy</subject><subject>Muscular Dystrophy, Duchenne - blood</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Muscular Dystrophy, Duchenne - pathology</subject><subject>Myoblasts - drug effects</subject><subject>Myoblasts - metabolism</subject><subject>Myoblasts - pathology</subject><subject>Ossification, Heterotopic - blood</subject><subject>Ossification, Heterotopic - metabolism</subject><subject>Ossification, Heterotopic - pathology</subject><subject>Osteocalcin - metabolism</subject><subject>Phosphates - blood</subject><subject>Phosphates - metabolism</subject><subject>skeletal muscle</subject><issn>0386-7196</issn><issn>1347-3700</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90U9rFDEYBvAgil2rB7-ABATFw9T8m2RyEllWLWxRUE8ewjuZN90sszPbZKbYb2-6u1jw4CUJb355IDyEvOTsggtl3vscLljDpH1EFlwqU0nD2GOyYLLRleFWn5FnOW8ZEzXT5ik5KyMhGiMX5NfKT-M-erqE3scQPUxxHGjMZTBn7Gh7R1c93sJUzmu8xT7TMdDvmOYdvRzGdA1Def1tM-b9piAaB3rV_aZX0eNz8iRAn_HFaT8nPz-tfiy_VOuvny-XH9eV18xMFSojggXWdlAHo7FGr0GLzisQgKDbAA2oulFoBTQ6gLDc1krZxrdMBCHPydtj7j6NNzPmye1i9tj3MOA4Z2ekYlwrWRf55r9SMMMsV7bA1__A7TinofzCcVXb2nAjZFHvjsqnMeeEwe1T3EG6c5y5-2ZcacYdmin21SlxbnfYPchTFQV8OIJtnuAa_wJIU_Q9HqKkcuJ-OUQ-3GwgORzkHxClnsE</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Kikkawa, Namiko</creator><creator>Ohno, Tomohisa</creator><creator>Nagata, Yosuke</creator><creator>Shiozuka, Masataka</creator><creator>Kogure, Toshihiro</creator><creator>Matsuda, Ryoichi</creator><general>Japan Society for Cell Biology</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090101</creationdate><title>Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice</title><author>Kikkawa, Namiko ; Ohno, Tomohisa ; Nagata, Yosuke ; Shiozuka, Masataka ; Kogure, Toshihiro ; Matsuda, Ryoichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-e472f9a0bda5f76e5ec6a62dc4a2aea6bfa8a4584e92a86fa291954498cb02f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Calcinosis - blood</topic><topic>Calcinosis - metabolism</topic><topic>Calcinosis - pathology</topic><topic>Cell Line</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>Disease Models, Animal</topic><topic>ectopic calcification</topic><topic>Fibroblast Growth Factors - blood</topic><topic>Hydroxyapatites - blood</topic><topic>Hydroxyapatites - metabolism</topic><topic>inorganic phosphate</topic><topic>mdx mouse</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred mdx</topic><topic>Microscopy, Electron, Scanning</topic><topic>Microscopy, Electron, Transmission</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - ultrastructure</topic><topic>muscular dystrophy</topic><topic>Muscular Dystrophy, Duchenne - blood</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Muscular Dystrophy, Duchenne - pathology</topic><topic>Myoblasts - drug effects</topic><topic>Myoblasts - metabolism</topic><topic>Myoblasts - pathology</topic><topic>Ossification, Heterotopic - blood</topic><topic>Ossification, Heterotopic - metabolism</topic><topic>Ossification, Heterotopic - pathology</topic><topic>Osteocalcin - metabolism</topic><topic>Phosphates - blood</topic><topic>Phosphates - metabolism</topic><topic>skeletal muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kikkawa, Namiko</creatorcontrib><creatorcontrib>Ohno, Tomohisa</creatorcontrib><creatorcontrib>Nagata, Yosuke</creatorcontrib><creatorcontrib>Shiozuka, Masataka</creatorcontrib><creatorcontrib>Kogure, Toshihiro</creatorcontrib><creatorcontrib>Matsuda, Ryoichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell Structure and Function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kikkawa, Namiko</au><au>Ohno, Tomohisa</au><au>Nagata, Yosuke</au><au>Shiozuka, Masataka</au><au>Kogure, Toshihiro</au><au>Matsuda, Ryoichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice</atitle><jtitle>Cell Structure and Function</jtitle><addtitle>Cell Struct. Funct.</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>34</volume><issue>2</issue><spage>77</spage><epage>88</epage><pages>77-88</pages><issn>0386-7196</issn><eissn>1347-3700</eissn><abstract>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. 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| subjects | Animals Calcinosis - blood Calcinosis - metabolism Calcinosis - pathology Cell Line Core Binding Factor Alpha 1 Subunit - metabolism Disease Models, Animal ectopic calcification Fibroblast Growth Factors - blood Hydroxyapatites - blood Hydroxyapatites - metabolism inorganic phosphate mdx mouse Mice Mice, Inbred C57BL Mice, Inbred mdx Microscopy, Electron, Scanning Microscopy, Electron, Transmission Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscle, Skeletal - ultrastructure muscular dystrophy Muscular Dystrophy, Duchenne - blood Muscular Dystrophy, Duchenne - metabolism Muscular Dystrophy, Duchenne - pathology Myoblasts - drug effects Myoblasts - metabolism Myoblasts - pathology Ossification, Heterotopic - blood Ossification, Heterotopic - metabolism Ossification, Heterotopic - pathology Osteocalcin - metabolism Phosphates - blood Phosphates - metabolism skeletal muscle |
| title | Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice |
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