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Altered bone development in a mouse model of peripheral sensory nerve inactivation
M A Heffner1, M J Anderson, G C Yeh
1University of California-Davis Medical Center, Department of Orthopaedic Surgery.
Objectives:
The present study sought to determine the effects of decreased peripheral sensory nerve function on skeletal development and bone metabolism in mice.
Methods:
C57BL/6 neonatal mice were treated with capsaicin to induce peripheral sensory nerve degeneration, and compared to vehicle-treated controls at 4, 8 and 12 weeks of age. Changes in bone structure were assessed using micro-computed tomography, mechanical properties and fracture resistance were assessed using three-point bending of radii, and bone turnover was assessed using dynamic histomorphometry and serum biomarkers.
Results:
Capsaicin treatment resulted in small but significant decreases in bone structure, particularly affecting trabecular bone. Capsaicin-treated mice exhibited lower trabecular thickness at the femoral metaphysis and L5 vertebral body compared with vehicle-treated mice. However, capsaicin- and vehicle-treated mice had similar mechanical properties and bone turnover rates.
Conclusion:
Neonatal capsaicin treatment affected trabecular bone during development; however these small changes may not be meaningful with respect to bone strength under normal loading conditions. It is possible that capsaicin-sensitive neurons may be more important for bone under stress conditions such as increased mechanical loading or injury. Future studies will investigate this potential role of peripheral sensory nerves in bone adaptation.
Insights
Decreased peripheral sensory nerve function in mice led to minor changes in trabecular bone structure during development. These alterations did not significantly impact bone strength under normal conditions, suggesting a role in stress responses.
Area of Science:
- Neuroscience
- Skeletal Biology
- Bone Metabolism
Background:
- Peripheral sensory nerves play a role in regulating bone metabolism and skeletal development.
- Understanding the specific contribution of these nerves is crucial for developing targeted therapies for bone disorders.
Purpose of the Study:
- To investigate the impact of reduced peripheral sensory nerve function on skeletal development and bone metabolism.
- To determine if capsaicin-induced nerve degeneration affects bone structure, mechanical properties, and turnover rates in mice.
Main Methods:
- Neonatal C57BL/6 mice received capsaicin to induce sensory nerve degeneration, compared to vehicle controls.
- Bone structure analyzed via micro-computed tomography.
- Mechanical properties assessed using three-point bending.
- Bone turnover evaluated through histomorphometry and serum biomarkers.
Main Results:
- Capsaicin treatment caused minor but significant reductions in trabecular bone structure, specifically affecting trabecular thickness in the femoral metaphysis and L5 vertebral body.
- No significant differences were observed in mechanical properties or bone turnover rates between capsaicin-treated and control groups.
Conclusions:
- Neonatal sensory nerve degeneration impacts trabecular bone development but may not compromise bone strength under normal loading.
- Capsaicin-sensitive neurons might be more critical for bone adaptation during stress, such as increased loading or injury.
- Further research is warranted to explore the role of peripheral sensory nerves in bone adaptation to stress.

