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Bone adaptation to mechanical loading in a mouse model of reduced peripheral sensory nerve function.

  • Author(s): Heffner, Mollie;
  • Genetos, Damian;
  • Christiansen, Blaine
  • et al.

Underlying mechanisms contributing to the imbalance in bone turnover during osteoporosis remain only partially explained. Reduced sensory nerve function may contribute to this imbalance, as sensory neuropeptides affect the activity of osteoblasts and osteoclasts in vivo, especially during bone adaptation. In this study, we investigated bone adaptation in mice following two weeks of tibial compression (peak magnitude 3 N or 7 N). To induce decreased sensory nerve function, mice were treated with capsaicin as neonates. We hypothesized that decreased sensory nerve function would diminish the adaptation of bone to mechanical loading, assessed with μCT and dynamic histomorphometry. We found that tibial compression induced significant changes in cortical microarchitecture that depended on compression magnitude and location along the length of the tibia; in contrast, there was no effect of loading on trabecular bone of the tibial metaphysis. Tibial compression significantly increased periosteal, and decreased endosteal, bone formation. Contrary to our initial hypothesis, capsaicin-treated mice generally displayed a similar, if not larger, adaptive response to mechanical loading, including greater increases in bone mineral content and mineral apposition rate. To integrate mechanical loading of bone with sensory nerve activation, we examined whether concentration of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in bone were affected following 1 or 5 days of 5 N tibial compression or hindlimb unloading. We found that 1 day of tibial compression significantly increased CGRP concentrations in bone, and hindlimb unloading also exhibited a trend toward increased CGRP in bone. These results may suggest a role of sensory nerves in the bone adaptation response to the mechanical environment, though this remains unclear.

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