Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues
During vertebrate skeletal development, osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix. Anoctamin6/Tmem16F (Ano6) belongs to a conserved family of transmembrane proteins with chloride channel properties. In addition, Ano6 has been l...
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| Veröffentlicht in: | Journal of bone and mineral research 2013-02, Vol.28 (2), p.246-259 |
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| creator | Ehlen, Harald WA Chinenkova, Milana Moser, Markus Munter, Hans‐Markus Krause, Yvonne Gross, Stefanie Brachvogel, Bent Wuelling, Manuela Kornak, Uwe Vortkamp, Andrea |
| description | During vertebrate skeletal development, osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix. Anoctamin6/Tmem16F (Ano6) belongs to a conserved family of transmembrane proteins with chloride channel properties. In addition, Ano6 has been linked to phosphatidylserine (PS) scrambling in the plasma membrane. During skeletogenesis, Ano6 mRNA is expressed in differentiating and mature osteoblasts. Deletion of Ano6 in mice results in reduced skeleton size and skeletal deformities. Molecular analysis revealed that chondrocyte and osteoblast differentiation are not disturbed. However, mutant mice display increased regions of nonmineralized, Ibsp‐expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally. In primary Ano6−/− osteoblasts, mineralization is delayed, indicating a cell autonomous function of Ano6. Furthermore, we demonstrate that calcium‐dependent PS scrambling is impaired in osteoblasts. Our study is the first to our knowledge to reveal the requirement of Ano6 in PS scrambling in osteoblasts, supporting a function of PS exposure in the deposition of hydroxyapatite. © 2013 American Society for Bone and Mineral Research |
| doi_str_mv | 10.1002/jbmr.1751 |
| format | Article |
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Anoctamin6/Tmem16F (Ano6) belongs to a conserved family of transmembrane proteins with chloride channel properties. In addition, Ano6 has been linked to phosphatidylserine (PS) scrambling in the plasma membrane. During skeletogenesis, Ano6 mRNA is expressed in differentiating and mature osteoblasts. Deletion of Ano6 in mice results in reduced skeleton size and skeletal deformities. Molecular analysis revealed that chondrocyte and osteoblast differentiation are not disturbed. However, mutant mice display increased regions of nonmineralized, Ibsp‐expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally. In primary Ano6−/− osteoblasts, mineralization is delayed, indicating a cell autonomous function of Ano6. Furthermore, we demonstrate that calcium‐dependent PS scrambling is impaired in osteoblasts. Our study is the first to our knowledge to reveal the requirement of Ano6 in PS scrambling in osteoblasts, supporting a function of PS exposure in the deposition of hydroxyapatite. © 2013 American Society for Bone and Mineral Research</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.1751</identifier><identifier>PMID: 22936354</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Animals, Newborn ; ANOCTAMIN ; Anoctamins ; Biological Transport ; Bone and Bones - metabolism ; Bone matrix ; Calcification, Physiologic ; Calcium ; Cells, Cultured ; Chloride channels ; Chondrocytes ; Crystals ; Embryo, Mammalian - metabolism ; Embryo, Mammalian - pathology ; Embryogenesis ; Extracellular matrix ; Hydroxyapatite ; Membrane proteins ; Mice ; Mice, Mutant Strains ; MINERALIZATION ; mRNA ; OSTEOBLAST ; Osteoblastogenesis ; Osteoblasts ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Osteoid ; Periosteum ; Phenotype ; phosphatidylserine ; Phosphatidylserines - metabolism ; PHOSPHOLIPID SCRAMBLING ; Phospholipid Transfer Proteins - deficiency ; Phospholipid Transfer Proteins - metabolism ; Plasma membranes ; SKELETAL DEVELOPMENT ; Skeletogenesis ; Skeleton ; Skull - pathology</subject><ispartof>Journal of bone and mineral research, 2013-02, Vol.28 (2), p.246-259</ispartof><rights>Copyright © 2013 American Society for Bone and Mineral Research</rights><rights>Copyright © 2013 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4871-d99824b8f523bab49076a67518475fe39a1e0b06683ee4ca63f6b273bd107e953</citedby><cites>FETCH-LOGICAL-c4871-d99824b8f523bab49076a67518475fe39a1e0b06683ee4ca63f6b273bd107e953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.1751$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.1751$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22936354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ehlen, Harald WA</creatorcontrib><creatorcontrib>Chinenkova, Milana</creatorcontrib><creatorcontrib>Moser, Markus</creatorcontrib><creatorcontrib>Munter, Hans‐Markus</creatorcontrib><creatorcontrib>Krause, Yvonne</creatorcontrib><creatorcontrib>Gross, Stefanie</creatorcontrib><creatorcontrib>Brachvogel, Bent</creatorcontrib><creatorcontrib>Wuelling, Manuela</creatorcontrib><creatorcontrib>Kornak, Uwe</creatorcontrib><creatorcontrib>Vortkamp, Andrea</creatorcontrib><title>Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>During vertebrate skeletal development, osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix. Anoctamin6/Tmem16F (Ano6) belongs to a conserved family of transmembrane proteins with chloride channel properties. In addition, Ano6 has been linked to phosphatidylserine (PS) scrambling in the plasma membrane. During skeletogenesis, Ano6 mRNA is expressed in differentiating and mature osteoblasts. Deletion of Ano6 in mice results in reduced skeleton size and skeletal deformities. Molecular analysis revealed that chondrocyte and osteoblast differentiation are not disturbed. However, mutant mice display increased regions of nonmineralized, Ibsp‐expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally. In primary Ano6−/− osteoblasts, mineralization is delayed, indicating a cell autonomous function of Ano6. Furthermore, we demonstrate that calcium‐dependent PS scrambling is impaired in osteoblasts. Our study is the first to our knowledge to reveal the requirement of Ano6 in PS scrambling in osteoblasts, supporting a function of PS exposure in the deposition of hydroxyapatite. © 2013 American Society for Bone and Mineral Research</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>ANOCTAMIN</subject><subject>Anoctamins</subject><subject>Biological Transport</subject><subject>Bone and Bones - metabolism</subject><subject>Bone matrix</subject><subject>Calcification, Physiologic</subject><subject>Calcium</subject><subject>Cells, Cultured</subject><subject>Chloride channels</subject><subject>Chondrocytes</subject><subject>Crystals</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryo, Mammalian - pathology</subject><subject>Embryogenesis</subject><subject>Extracellular matrix</subject><subject>Hydroxyapatite</subject><subject>Membrane proteins</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>MINERALIZATION</subject><subject>mRNA</subject><subject>OSTEOBLAST</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoblasts - pathology</subject><subject>Osteoid</subject><subject>Periosteum</subject><subject>Phenotype</subject><subject>phosphatidylserine</subject><subject>Phosphatidylserines - metabolism</subject><subject>PHOSPHOLIPID SCRAMBLING</subject><subject>Phospholipid Transfer Proteins - deficiency</subject><subject>Phospholipid Transfer Proteins - metabolism</subject><subject>Plasma membranes</subject><subject>SKELETAL DEVELOPMENT</subject><subject>Skeletogenesis</subject><subject>Skeleton</subject><subject>Skull - pathology</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EokNhwQsgS2xAajp27PhnCVWBoiIkVNaRndy0Hpw4tR2q2fEIvAAvx5Pg6RQWSIjVla6-e47uOQg9peSYElKvN3aMx1Q29B5a0aZmFReK3kcrohSvCGf0AD1KaUMIEY0QD9FBXWsmWMNX6MfZZLrsvprswoTDgM0UumxGN_389l2sL0YYqRiOsMERLhdvcog7ar4Kab4qR_3WJ4huApy6aEbr3XSJXVFKGYL1JuV0hD2YPuEccA9dBJOgx8UAovFlM4fkbs3LVfoCHnJZZ5fSAukxejCYYvDkbh6iz29OL07eVecf356dvDqvOq4krXqtVc2tGsrv1liuiRRGlDwUl80ATBsKxBIhFAPgnRFsELaWzPaUSNANO0Qv9rpzDNfFN7ejSx14byYIS2ppramgqilZ_h-VrFFEEl3Q53-hm7DEqTxSKKG5VEzIQr3cU10MKUUY2jm60cRtS0m7q7fd1dvu6i3sszvFxY7Q_yF_91mA9R64cR62_1Zq37_-8OlW8hc9v7HM</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Ehlen, Harald WA</creator><creator>Chinenkova, Milana</creator><creator>Moser, Markus</creator><creator>Munter, Hans‐Markus</creator><creator>Krause, Yvonne</creator><creator>Gross, Stefanie</creator><creator>Brachvogel, Bent</creator><creator>Wuelling, Manuela</creator><creator>Kornak, Uwe</creator><creator>Vortkamp, Andrea</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley Subscription Services, Inc</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>7TS</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201302</creationdate><title>Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues</title><author>Ehlen, Harald WA ; Chinenkova, Milana ; Moser, Markus ; Munter, Hans‐Markus ; Krause, Yvonne ; Gross, Stefanie ; Brachvogel, Bent ; Wuelling, Manuela ; Kornak, Uwe ; Vortkamp, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4871-d99824b8f523bab49076a67518475fe39a1e0b06683ee4ca63f6b273bd107e953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>ANOCTAMIN</topic><topic>Anoctamins</topic><topic>Biological Transport</topic><topic>Bone and Bones - metabolism</topic><topic>Bone matrix</topic><topic>Calcification, Physiologic</topic><topic>Calcium</topic><topic>Cells, Cultured</topic><topic>Chloride channels</topic><topic>Chondrocytes</topic><topic>Crystals</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryo, Mammalian - pathology</topic><topic>Embryogenesis</topic><topic>Extracellular matrix</topic><topic>Hydroxyapatite</topic><topic>Membrane proteins</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>MINERALIZATION</topic><topic>mRNA</topic><topic>OSTEOBLAST</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Osteoid</topic><topic>Periosteum</topic><topic>Phenotype</topic><topic>phosphatidylserine</topic><topic>Phosphatidylserines - metabolism</topic><topic>PHOSPHOLIPID SCRAMBLING</topic><topic>Phospholipid Transfer Proteins - deficiency</topic><topic>Phospholipid Transfer Proteins - metabolism</topic><topic>Plasma membranes</topic><topic>SKELETAL DEVELOPMENT</topic><topic>Skeletogenesis</topic><topic>Skeleton</topic><topic>Skull - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ehlen, Harald WA</creatorcontrib><creatorcontrib>Chinenkova, Milana</creatorcontrib><creatorcontrib>Moser, Markus</creatorcontrib><creatorcontrib>Munter, Hans‐Markus</creatorcontrib><creatorcontrib>Krause, Yvonne</creatorcontrib><creatorcontrib>Gross, Stefanie</creatorcontrib><creatorcontrib>Brachvogel, Bent</creatorcontrib><creatorcontrib>Wuelling, Manuela</creatorcontrib><creatorcontrib>Kornak, Uwe</creatorcontrib><creatorcontrib>Vortkamp, Andrea</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>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ehlen, Harald WA</au><au>Chinenkova, Milana</au><au>Moser, Markus</au><au>Munter, Hans‐Markus</au><au>Krause, Yvonne</au><au>Gross, Stefanie</au><au>Brachvogel, Bent</au><au>Wuelling, Manuela</au><au>Kornak, Uwe</au><au>Vortkamp, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2013-02</date><risdate>2013</risdate><volume>28</volume><issue>2</issue><spage>246</spage><epage>259</epage><pages>246-259</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>During vertebrate skeletal development, osteoblasts produce a mineralized bone matrix by deposition of hydroxyapatite crystals in the extracellular matrix. Anoctamin6/Tmem16F (Ano6) belongs to a conserved family of transmembrane proteins with chloride channel properties. In addition, Ano6 has been linked to phosphatidylserine (PS) scrambling in the plasma membrane. During skeletogenesis, Ano6 mRNA is expressed in differentiating and mature osteoblasts. Deletion of Ano6 in mice results in reduced skeleton size and skeletal deformities. Molecular analysis revealed that chondrocyte and osteoblast differentiation are not disturbed. However, mutant mice display increased regions of nonmineralized, Ibsp‐expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally. In primary Ano6−/− osteoblasts, mineralization is delayed, indicating a cell autonomous function of Ano6. Furthermore, we demonstrate that calcium‐dependent PS scrambling is impaired in osteoblasts. Our study is the first to our knowledge to reveal the requirement of Ano6 in PS scrambling in osteoblasts, supporting a function of PS exposure in the deposition of hydroxyapatite. © 2013 American Society for Bone and Mineral Research</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22936354</pmid><doi>10.1002/jbmr.1751</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Animals, Newborn ANOCTAMIN Anoctamins Biological Transport Bone and Bones - metabolism Bone matrix Calcification, Physiologic Calcium Cells, Cultured Chloride channels Chondrocytes Crystals Embryo, Mammalian - metabolism Embryo, Mammalian - pathology Embryogenesis Extracellular matrix Hydroxyapatite Membrane proteins Mice Mice, Mutant Strains MINERALIZATION mRNA OSTEOBLAST Osteoblastogenesis Osteoblasts Osteoblasts - metabolism Osteoblasts - pathology Osteoid Periosteum Phenotype phosphatidylserine Phosphatidylserines - metabolism PHOSPHOLIPID SCRAMBLING Phospholipid Transfer Proteins - deficiency Phospholipid Transfer Proteins - metabolism Plasma membranes SKELETAL DEVELOPMENT Skeletogenesis Skeleton Skull - pathology |
| title | Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues |
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