Normal bone deposition occurs in mice deficient in Factor XIII-A and Transglutaminase 2

Paul A. Cordell, Laura M. Newell, Kristina F. Standeven, Penelope J. Adamson, Kingsley R. Simpson, Kerrie A. Smith, Christopher L. Jackson, Peter J. Grant, Richard J. Pease

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Transglutaminase activity has been widely implicated in bone deposition. A predominant role has been proposed for factor (F)XIII-A and a subsidiary role suggested for the homologous protein, transglutaminase 2. Full-length FXIII-A is an 83kDa protransglutaminase that is present both in plasma and also in haematopoietic and connective tissue lineages. Several studies have reported expression in murine cells, including osteocytes, of a 37kDa protein that reacts with the monoclonal anti-FXIII-A antibody AC-1A1. This protein was presumed to be a catalytically active fragment of FXIII-A-83 and to play a major role in bone deposition. 

We detected a 37kDa AC-1A1 reactive protein in FXIII-A mRNA negative cell lines and in tissues from FXIII-A-/- mice. By mass spectrometric sequencing of AC-1A1 immunoprecipitates, we identified this protein as transaldolase-1, and confirmed that recombinant transaldolase-1 is recognised by AC-1A1. We have also shown that bone deposition is normal in FXIII-A-/-.TG2-/- double knockout mice, casting doubt on the role of transglutaminases in bone mineralisation. Various studies have used antibody AC-1A1 for immunohistochemistry or immunofluorescence. We observe strong FXIII-A dependent staining in paraffin embedded mouse heart sections, with relatively low background in non-expressing mouse cells. In contrast, FXIII-A independent staining predominates in cultured human cells using a standard immunofluorescence procedure. Immunofluorescence is present in membrane compartments that are expected to lack transaldolase, indicating that other off-target antigens are recognised by AC-1A1. 

This has significant implications for studies that have used this approach to define the subcellular trafficking of FXIII-A in osteocytes.

Original languageEnglish
Pages (from-to)85-96
Number of pages12
JournalMatrix Biology
Publication statusPublished - 1 Apr 2015
Externally publishedYes


  • Antibodies
  • Bone development
  • Mice
  • Transaldolase
  • Transglutaminases


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