2021 Volume No 41 – pages 345-354
Title: Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1 |
Authors: T-Y Liu, M Bartnikowski, AC Wu, M Veitch, KA Sokolowski, SM Millard, AR Pettit, V Glatt, CH Evans, JW Wells |
Address: The University of Queensland Diamantina Institute, 37 Kent Street,
Woolloongabba, QLD 4102, Australia |
E-mail: j.wells3 at uq.edu.au |
Abstract: Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a
substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced
by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter
in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed
whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved
drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain
groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using
an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was
monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic
and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or
duration. A comparison of healed C57BL/6 and Rag1−/− femora by µCT and ex vivo torsion testing showed
no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume
ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role
for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions. |
Key Words: Tacrolimus, FK506, bone healing, immunosuppression, local administration, mouse. |
Publication date: March 17th 2021 |
Article download: Pages
345-354 (PDF file) |
