Different effects of Wnt/β‐catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice

Abstract

Summary Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/β‐catenin signalling are two promising anabolic anti‐osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of β‐catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6‐mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and β‐catenin activation were used to observe the promoting effect on bone healing. The effects of β‐catenin and PTH signalling on fracture healing were observed by X‐ray and CT at 3, 6, and 14 days after fracture, and the levels of β‐catenin were detected by RT‐PCR assay, and the number of specific antigen‐positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While β‐catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of β‐catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.

Wnt/β-catenin signalling promotes more effective fracture healing in aged mice than in adult mice by inducing angiogenesis and cell differentiation

“…TM, saline and 5′-bromo-2-deoxyuridine were intraperitoneally injected using the methods described in a previous study. 18 …”

“… 16 The regions of interest (ROI) and calculations were performed as described in a previous study. 18 …”

“…16 The regions of interest (ROI) and calculations were performed as described in a previous study. 18 Quantitative morphometric data were based on the region of interest as follows: a diameter of 0.8 mm was taken at the defect centre with a depth of 0.4 mm. The percentage of bone volume to total volume (BV/TV) was calculated for the bone injury sites.…”

A novel mouse model to study fracture healing of the proximal femur

“…Further studies demonstrate different effects of both antiresorptive and osteoanabolic treatment strategies including Wnt/β-catenin activation, parathyroid hormone application, and bisphosphonate injections on metaphyseal and diaphyseal bone healing. 5,6 Therefore, metaphyseal osteoporotic fractures require more complex strategies to facilitate optimal bone healing. This is especially true for osteoporotic hip fractures, which occur mainly in the region of the femoral neck and the femoral trochanter and are therefore classified as metaphyseal fractures.…”

“…Most of these studies used drill hole defects in the mouse femur or tibia. [4][5][6][7]14 However, drill hole defects lack biomechanical stimulation at the fracture site and furthermore, no fracture implants are used for this approach. This might critically influence the type of healing.…”