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 8 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.

Mice with a heterozygous Lrp6 deletion have impaired fracture healing

“… 36 As healing progresses, the interior of the callus also loses its density as the mature bone concentrates on the periosteal surface. 35 The empty (not mineralized) area in the callus was approximately doubled in the Lrp6 +/− group at day 14 PF. This increase in the empty area decreased the total callus density and BV/TV in the Lrp6 +/− group.…”

“…In Mimics, two transverse slices were used to analyze the bone maturity level of each callus (see Burgers et al 32 and Collins et al 35 for similar examples). The center of the callus was determined as the location of the small gap between the bones.…”

miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury

“…PI3K/AKT signaling is a cell-growth-regulatory pathway involved in many diseases 52, 53. Previous studies54, 55 suggested that this pathway is essential for the differentiation of bone progenitor cells.…”

Inhibiting checkpoint kinase 1 protects bone from bone resorption by mammary tumor in a mouse model

“…The tibia and femur were loaded to failure by four-point bending using Electro Force 3100 (Bose, Inc.) [ 50 ]. After applying a 0.5-N preload, the bone was loaded monotonically at 0.03 mm/s.…”