Thymosin β4 administration enhances fracture healing in mice

Rhys D. Brady, Brian L. Grills, Johannes A. Schuijers, Alex R. Ward, Brett A. Tonkin, Nicole C. Walsh, Stuart J. McDonald

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Thymosin β4 (Tβ4) is a regenerative peptide that we hypothesized would promote healing of fractured bone. Mice received a bilateral fibular osteotomy and were given i.p. injections of either Tβ4 (6mg/kg) or saline. Calluses from saline- and Tβ4-treated mice were analyzed for: (1) biomechanical properties and (2) composition using micro-computed tomography (μCT) and histomorphometry. Biomechanical analysis showed that Tβ4-treated calluses had a 41% increase in peak force to failure (p<0.01) and were approximately 25% stiffer (p<0.05) than saline-treated controls. μCT analysis at 21 days post-fracture showed that the fractional volume of new mineralized tissue and new highly mineralized tissue were respectively 18% and 26% greater in calluses from Tβ4-treated mice compared to controls (p<0.01; p<0.05, respectively). Histomorphometry complemented the μCT data; at 21 days post-fracture, Tβ4-treated calluses were almost 23% smaller (p<0.05), had nearly 47% less old cortical bone (p<0.05) and had a 31% increase in new trabecular bone area/total callus area fraction compared with controls (p<0.05). Our finding of enhanced biomechanical properties of fractures in mice treated with Tβ4 provides novel evidence of the therapeutic potential of this peptide for treating bone fractures.

Original languageEnglish
Pages (from-to)1277-1282
Number of pages6
JournalJournal of Orthopaedic Research
Issue number10
Publication statusPublished - 1 Jan 2014
Externally publishedYes


  • bone regeneration
  • fracture healing
  • mice

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