title: Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis.
abstract: Previous studies have shown that a single injection of thrombin peptide (TP508) accelerates fracture repair in a closed rat femoral fracture model. The present study was conducted to elucidate the molecular mechanisms of TP508 action using Affymetrix genome-scale profiling and to link early gene expression changes to fracture histology and bone strength changes. Treatment of femoral fractures with TP508 accelerated fracture repair as determined by destructive torsion testing. Blinded histological analysis demonstrated that TP508-treated fracture callus had a significant increase in blood vessels relative to the controls. Gene array analysis showed that TP508 significantly induced expression of early growth factors, inflammatory response modifiers, and angiogenesis-related genes. This study therefore suggests that TP508 promotes fracture repair through a mechanism that involves an increased induction of a number of growth factors, enhanced expression of inflammatory mediators, and angiogenesis-related genes.
authors.affiliation: Research and Development, OrthoLogic Corp, Tempe, AZ 85281, USA. hwang@olgc.com
authors.forename: Hali
authors.initials: H
authors.lastname: Wang
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Emre
authors.initials: E
authors.lastname: Tomin
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Doty
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lane
authors.forename: Darrell H
authors.initials: DH
authors.lastname: Carney
authors.forename: James T
authors.initials: JT
authors.lastname: Ryaby
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D017102:Fracture Healing / Q000187:drug effects*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D006133:Growth Substances; D018836:Inflammation Mediators; D010446:Peptide Fragments; C412222:rusalatide acetate; D013917:Thrombin