title: 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 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.
authors.affiliation: University of Wisconsin-Madison, Department of Mechanical Engineering, Madison, WI, USA.
authors.forename: Caitlyn J
authors.initials: CJ
authors.lastname: Collins
authors.affiliation: University of Wisconsin-Madison, Department of Mechanical Engineering, Madison, WI, USA; Universidad Adolfo Ibáñez, Facultad de Ingeniería y Ciencias, Viña del Mar, Chile.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Vivanco
authors.affiliation: University of Wisconsin-Madison, Department of Mechanical Engineering, Madison, WI, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sokn
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Burgers
authors.affiliation: University of Wisconsin-Madison, Department of Mechanical Engineering, Madison, WI, USA. Electronic address: ploeg@engr.wisc.edu.
authors.forename: Heidi-Lynn
authors.initials: HL
authors.lastname: Ploeg
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D002146:Bony Callus / Q000378:metabolism; D005264:Femoral Fractures / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017102:Fracture Healing; D007091:Image Processing, Computer-Assisted; D055595:Mechanical Phenomena; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: D051059:PTEN Phosphohydrolase
keywords: Four-point bend testing; Fracture healing; Mechanical properties; Micro computed tomography image-based analysis; Mouse femur; Pten gene; Section properties