title: Thymosin β4 administration enhances fracture healing in mice.
abstract: 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 (6 mg/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.
authors.affiliation: Department of Human Biosciences, La Trobe University, Victoria, Australia.
authors.forename: Rhys D
authors.initials: RD
authors.lastname: Brady
authors.forename: Brian L
authors.initials: BL
authors.lastname: Grills
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Schuijers
authors.forename: Alex R
authors.initials: AR
authors.lastname: Ward
authors.forename: Brett A
authors.initials: BA
authors.lastname: Tonkin
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Walsh
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McDonald
mesh_terms: D000818:Animals; D005360:Fibula / Q000293:injuries; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D050723:Fractures, Bone / Q000188:drug therapy / Q000628:therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D055595:Mechanical Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013947:Thymosin / Q000008:administration & dosage* / Q000627:therapeutic use; D000099201:Thymosin beta(4)
chemical_list: D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: bone regeneration; fracture healing; mice; thymosin β4