Stimulation of EP4 receptor enhanced bone consolidation during distraction osteogenesis

Abstract

The objective of this study was to confirm whether an agonist of prostaglandin E receptor subtype EP4 can enhance bone consolidation in distraction osteogenesis. A rat distraction osteogenesis model was generated. A unilateral external fixator was fixed to the left femur of the rats of this model after osteotomy. Seven days later, 0.25 mm/12 h or 0.5 mm/12 h elongation was performed for 2 weeks. A systemic administration of an EP4 receptor agonist (ONO 4819 Á CD, 3, 10, 30 mg/kg) or normal saline by subcutaneous injection was also performed for 2 weeks. The animals were sacrificed 10, 14, 17, 21, and 42 days after the operation. Radiographic examination, histological examination, and measurements of bone mineral density (BMD) and distraction-callus hardness were performed to qualitatively and quantitatively evaluate new bone formation. Twenty-one days after the operation, the experimental group had a higher BMD and a higher distraction-callus hardness than that of the control group. Forty-two days after the operation, BMD was similar among all of the groups. But the hardness of the experimental groups increased more than that of the control group, so the statistical differences in distraction-callus hardness became more distinct between the two groups, indicating an improved remodeling of the distraction callus. These findings are also supported by histological examination. Subcutaneous injection of an EP4 receptor agonist can promote bone formation and remodeling during distraction osteogenesis. ONO 4819 Á CD might be a potential candidate for shortening the treatment time of distraction osteogenesis. ß

Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction OsteogenesisviaEndochondral Bone Formation

“… 10) Since the biological mechanism of DO has been studied deeply, several materials have been investigated to reduce the duration of DO. Enhancement of bone formation has been attempted using various materials including mesenchymal stem cells, 11 12) bone morphogenetic protein (BMP), 13 14 15) fibroblast growth factor, 16) prostaglandin E receptor agonist, 17) and bone conduction agents such as calcium sulfate. 18) However, these materials have limitations in terms of accessibility, high cost, short duration of effect and/or low effectiveness.…”

Mechanical Characterization at the Microscale of Mineralized Bone Callus after Bone Lengthening

“…We could link these observations with descriptions of the bone regenerative process in the literature. The outer edge of the distracted callus tends to form tissue with cortical-like bone properties during the consolidation phase of DO [56]. Moreover, if we looked at the hardness, the only differences seen at 59-DPS were inside ROIs of the periosteal callus.…”

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur

“…October 2017 | 128 | e56433 | Page 2 of 8 clearly demonstrate the efficiency of their protocols in obtaining a functional regenerated bone 7,16 . It is therefore difficult to compare results from various DO studies, due to their differing protocols and lack of information regarding the external fixator 12,13,14,17 . Thus, the aim of this study was to describe, in a rat model, an efficient and reproducible protocol for DO on the femur that leads to a functional regenerated bone.…”