Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur

Abstract In the United States, approximately eight million osseous fractures are reported annually, of which 5–10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks i...

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Bibliographic Details
Published in:	Journal of biomechanics Vol. 48; no. 2; pp. 310 - 317
Main Authors:	Collins, Caitlyn J, Vivanco, Juan F, Sokn, Scott A, Williams, Bart O, Burgers, Travis A, Ploeg, Heidi-Lynn
Format:	Journal Article
Language:	English
Published:	United States Elsevier Ltd 21-01-2015 Elsevier Limited
Subjects:	Animals Biomechanical Phenomena Bone Density Bones Bony Callus - metabolism Failure Femoral Fractures - diagnostic imaging Femoral Fractures - metabolism Femoral Fractures - pathology Femoral Fractures - physiopathology Femur Femur - diagnostic imaging Femur - metabolism Femur - pathology Femur - physiopathology Four-point bend testing Fracture Healing Fracture mechanics Genes Geometry Healing Image Processing, Computer-Assisted Mechanical Phenomena Mechanical properties Methods Mice Mice, Knockout Micro computed tomography image-based analysis Mouse femur Organ Size Osteoblasts Osteoblasts - metabolism Physical Medicine and Rehabilitation Pten gene PTEN Phosphohydrolase - deficiency PTEN Phosphohydrolase - genetics Section properties Software Stiffness Studies X-Ray Microtomography Pten gene Micro computed tomography image-based analysis Four-point bend testing Section properties Mechanical properties Fracture healing Mouse femur
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Summary:	Abstract In the United States, approximately eight million osseous fractures are reported annually, of which 5–10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (μCT) scanner (Skyscan, Kontich, Belgium). The present study used µCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9290 1873-2380
DOI:	10.1016/j.jbiomech.2014.11.028