New insights into the location and form of sclerostin

Paula Hernandez, Ciara Whitty, R. John Wardale, Frances M.D. Henson

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Sclerostin is widely reported to be a monomeric osteocyte specific protein. In this study we have investigated whether sclerostin is produced in different forms and in which cell and tissue types they are produced. We have demonstrated that recombinant sclerostin is composed of monomers and dimers, and that these, and other forms, notably 46 and 70 kDa forms, are found widely throughout the musculo-skeletal system. We have shown that 'dimeric' sclerostin is highly resistant to reduction, implying the presence of highly stable, non-reducible covalent bonds. We have also demonstrated that the form of sclerostin is not associated with the mineralisation state of the tissue or cell. Sclerostin was secreted by bone explants as high molecular weight forms that were reducible to the dimeric form. This dimeric form was detected in sera and in non-skeletal soft tissues specifically kidney, live, heart and lung. We therefore hypothesise: (a) sclerostin exists in multiple forms not associated with the mineralised state of the cell/tissue and (b) circulating sclerostin is dimeric, as is the sclerostin found in non-musculoskeletal soft tissues these observations may have significant implications for the therapeutic modulation of sclerostin.

Original languageEnglish (US)
Pages (from-to)1108-1113
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume446
Issue number4
DOIs
StatePublished - Apr 18 2014
Externally publishedYes

Keywords

  • Bone
  • Cartilage
  • Sclerostin
  • Wnt

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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