Bone formation is enhanced by thrombin‐related peptide TP508 during distraction osteogenesis

Abstract

The thrombin-related peptide, TP508, has been shown to promote soft tissue healing and fracture repair. One possible clinical application of TP508 is to accelerate bone regeneration during distraction osteogenesis, which is a lengthy procedure involving significant complications. In this study, we tested the ability of TP508 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Twenty-three rabbits had left tibiae lengthened for 1 cm over a period of 6 days. T P 508 (0, 30 and 300 pg in 300 pI saline) was injected into the distraction gaps at the beginning and the end of the lengthening phase, and all the animals were killed 2 weeks after lengthening. By the end of experiment, more animals in the TP508 treated groups had complete bony union of the distraction gaps when compared to the saline treated group. pQCT examination of the regenerates demonstrated a significantly greater bone mineral density (BMD) in the TP508 treated groups relative to the saline control group, but no statistical difference in the BMD was found between the two dosages of TP508. Bone consolidation and bone remodeling was far advanced in the TP508 300 pg treated group, and the regenerates mainly consisted of well-vascularized woven bone. In contrast, in the group that received the 30 pg TP508 treatment, focal bone defects and discontinuities of the new cortices were evident in some but not all animals. In the saline control group a majority of the animals showed large amounts of fibrous and cartilaginous tissues in the regenerates, and none of the regenerates had completed consolidation. This study has demonstrated that local application of TP508 enhanced bone formation and consolidation during distraction osteogenesis in the rabbit. The findings indicate that TP508 may be useful in promoting osteogenesis in situations when augmentative treatment for bone formation and consolidation are needed.

Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

“…Thrombin, e.g., plays a key role for leukocyte and platelet activation and induces the formation of a fi brin matrix, which allows cell invasion and acts as a sustained release system for secreted cytokines and mitogens (Brass, 2003;Mosesson, 2005). Additionally, direct stimulatory potential of thrombin on osteogenesis has been reported (Karp et al, 2005;Li et al, 2005;Song et al, 2005;Wang et al, 2005;Pagel et al, 2006;Pagel et al, 2009 ). This strong relation between the activation of blood coagulation, acute infl ammation and osteogenesis suggests that thrombogenesis provides important stimuli for osseointegration of endosseous implants (Stanford, 2010).…”

Effects of calcitonin and alendronate on distraction osteogenesis

“…Li et al found that recombinant human bone morphogenetic protein -2 (rhBMP-2) reinforced the consolidation phase of distraction osteogenesis in rabbit models and also enhanced volumetric density [15]. Li et al also revealed that thrombin-related peptide (TP 508) enhanced bone formation and the consolidation phase of distraction osteogenesis [16].…”

Augmentation of osseous phenotypes in vivo with a synthetic peptide

“…7 TP508 is a thrombinderived peptide with wide specificity that causes angiogenesis, cytokine release, and appears to act through activation of an inflammatory response. 4,8 P-15 is a collagen-derived high-affinity cell-binding peptide 9 which increases cell attachment and modulates a number of gene products. 10,11 The 73-92 peptide corresponds to residues 73-92 of the knuckle epitope of BMP-2, 7 and while it activates alkaline phosphatase, it also blocks BMP-2 binding to its receptors.…”