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Updated: Jan 28, 2026
The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing
Published on: August 16, 2018
The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in
Maddison R Johnstone1, Rhys D Brady, Johannes A Schuijers
1Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Australia.
Objectives:
To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on an osteoprogenitor cell line in vitro.
Methods:
Mice were given bilateral fibular fractures and treated for two weeks with vehicle or 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computed tomography (µCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM of GA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days.
Results:
µCT analysis found that 21-day GA-treated calluses had both decreased tissue volume (p<0.05) and bone surface (p<0.05) and increased fractional bone volume (p<0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed that GA treatment increased stiffness per unit area by 53% (p<0.01) and load per unit area by 52% (p<0.01). GA treatment increased Kusa O gene expression of alkaline phosphatase and osteocalcin (p<0.05) by 14 days as well as mineralization at 21 days (p<0.05).
Conclusions:
GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation and matrix mineralization.
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