Inactivation of anoctamin‐6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues. (15th January 2013)

• Record Type: Journal Article
• Authors: Ehlen, Harald WA; Chinenkova, Milana; Moser, Markus; Munter, Hans‐Markus; Krause, Yvonne; Gross, Stefanie; Brachvogel, Bent; Wuelling, Manuela; Kornak, Uwe; Vortkamp, Andrea
• Is Part Of: Journal of bone and mineral research. Volume 28:Number 2(2013:Feb.)
• Page Start: 246
• Page End: 259
• Publication Date: 2013-01-15
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.1751
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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, <italic>Ano6</italic> mRNA is expressed in differentiating and mature osteoblasts. Deletion of <italic>Ano6</italic> 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, <italic>Ibsp</italic>‐expressing osteoblasts in the periosteum during embryonic development and increased areas of uncalcified osteoid postnatally. In primary <italic>Ano6</italic>^{<italic>−/−</italic>} osteoblasts, mineralization is delayed, indicating a cell autonomous function of <italic>Ano6</italic>. 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 <italic>Ano6</italic> in PS scrambling in osteoblasts, supporting a function of PS exposure in the deposition of hydroxyapatite. © 2013 American Society for Bone and Mineral Research</p> </abstract>