Inactivation of Anoctamin-6/Tmem16f, a Regulator of Phosphatidylserine Scrambling in Osteoblasts, Leads to Decreased Mineral Deposition in Skeletal Tissues

被引：98

作者：

Ehlen, Harald W. A. ^{[1
,2
]}

Chinenkova, Milana ^{[1
,2
]}

Moser, Markus ^{[3
]}

Munter, Hans-Markus ^{[4
]}

Krause, Yvonne ^{[1
,2
]}

Gross, Stefanie ^{[1
,2
]}

Brachvogel, Bent ^{[5
,6
]}

Wuelling, Manuela ^{[1
,2
]}

Kornak, Uwe ^{[7
,8
]}

Vortkamp, Andrea ^{[1
,2
,4
]}

机构：

[1] Univ Duisburg Essen, Fac Biol, Dept Dev Biol, D-45117 Essen, Germany

[2] Univ Duisburg Essen, Ctr Med Biotechnol ZMB, D-45117 Essen, Germany

[3] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany

[4] Max Planck Inst Mol Genet, Otto Warburg Labs, D-14195 Berlin, Germany

[5] Univ Cologne, Ctr Biochem, Fac Med, D-50931 Cologne, Germany

[6] Univ Cologne, Ctr Mol Med CMMC, D-50931 Cologne, Germany

[7] Max Planck Inst Mol Genet, Dev & Dis Res Grp, D-14195 Berlin, Germany

[8] Charite, Inst Med Genet & Humangenet, D-13353 Berlin, Germany

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2013年 / 28卷 / 02期

关键词：

SKELETAL DEVELOPMENT; MINERALIZATION; ANOCTAMIN; PHOSPHOLIPID SCRAMBLING; OSTEOBLAST; COLLAGEN-BINDING GLYCOPROTEIN; ACTIVATED CHLORIDE CHANNEL; MATRIX VESICLES; BONE-FORMATION; TRANSMEMBRANE PROTEIN; ANCHORIN-CII; II COLLAGEN; GNATHODIAPHYSEAL-DYSPLASIA; CLEIDOCRANIAL DYSPLASIA; CHONDROCYTE MEMBRANES;

D O I：

10.1002/jbmr.1751

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2013 American Society for Bone and Mineral Research.

引用

页码：246 / 259

页数：14

共 77 条

[31] Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin [J].

Kolanczyk, Mateusz ;

Kuehnisch, Jirko ;

Kossler, Nadine ;

Osswald, Monika ;

Stumpp, Sabine ;

Thurisch, Boris ;

Kornak, Uwe ;

Mundlos, Stefan .

BMC MEDICINE, 2008, 6 (1)

[32] Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts [J].

Komori, T ;

Yagi, H ;

Nomura, S ;

Yamaguchi, A ;

Sasaki, K ;

Deguchi, K ;

Shimizu, Y ;

Bronson, RT ;

Gao, YH ;

Inada, M ;

Sato, M ;

Okamoto, R ;

Kitamura, Y ;

Yoshiki, S ;

Kishimoto, T .

CELL, 1997, 89 (05) :755-764

[33] Phosphatidylserine peroxidation/externalization during staurosporine-induced apoptosis in HL-60 cells [J].

Matsura, T ;

Serinkan, BF ;

Jiang, JF ;

Kagan, VE .

FEBS LETTERS, 2002, 524 (1-3) :25-30

[34] Interaction of FGF, lhh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation [J].

Minina, E ;

Kreschel, C ;

Naski, MC ;

Ornitz, DM ;

Vortkamp, A .

DEVELOPMENTAL CELL, 2002, 3 (03) :439-449

[35] Molecular characterization of GDD1/TMEM16E, the gene product responsible for autosomal dominant gnathodiaphyseal dysplasia [J].

Mizuta, Kuniko ;

Tsutsumi, Satoshi ;

Inoue, Hiroshi ;

Sakamoto, Yukiko ;

Miyatake, Katsutoshi ;

Miyawaki, Katsuyuki ;

Noji, Sumihare ;

Kamata, Nobuyuki ;

Itakura, Mitsuo .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 357 (01) :126-132

[36] ISOLATION AND CHARACTERIZATION OF A COLLAGEN-BINDING GLYCOPROTEIN FROM CHONDROCYTE MEMBRANES [J].

MOLLENHAUER, J ;

VONDERMARK, K .

EMBO JOURNAL, 1983, 2 (01) :45-50

[37] ROLE OF ANCHORIN-CII, A 31,000-MOL-WT MEMBRANE-PROTEIN, IN THE INTERACTION OF CHONDROCYTES WITH TYPE-II COLLAGEN [J].

MOLLENHAUER, J ;

BEE, JA ;

LIZARBE, MA ;

VONDERMARK, K .

JOURNAL OF CELL BIOLOGY, 1984, 98 (04) :1572-1579

[38] Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia [J].

Mundlos, S ;

Otto, F ;

Mundlos, C ;

Mulliken, JB ;

Aylsworth, AS ;

Albright, S ;

Lindhout, D ;

Cole, WG ;

Henn, W ;

Knoll, JHM ;

Owen, MJ ;

Mertelsmann, R ;

Zabel, BU ;

Olsen, BR .

CELL, 1997, 89 (05) :773-779

[39]

Nakashima K, 2002, CELL, V108, P17, DOI 10.1016/S0092-8674(01)00622-5

[40] Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene [J].

Nishio, Yasuhiko ;

Dong, Yufeng ;

Paris, Mark ;

O'Keefe, Regis J. ;

Schwarz, Edward M. ;

Drissi, Hicham .

GENE, 2006, 372 :62-70

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