Trabecular Bone Microarchitecture Improvement Is Associated With Skeletal Nerve Increase Following Aerobic Exercise Training in Middle-Aged Mice

Abstract

Advancing age is associated with bone loss and an increased risk of osteoporosis. Exercise training improves bone metabolism and peripheral nerve regeneration, and may play a critical role in osteogenesis and increase in skeletal nerve fiber density. In this study, the potential positive role of aerobic exercise training in bone metabolism and skeletal nerve regeneration was comprehensively evaluated in 14-month-old male C57BL/6 mice. The mice were divided into two groups: no exercise (non-exercise group) and 8-weeks of aerobic exercise training (exercise group), with six mice in each group. Dual-energy X-ray absorptiometry and micro-computed tomography showed that femoral and tibial bone parameters improved after aerobic exercise training. Greater skeletal nerve fiber density was also observed in the distal femoral and proximal tibial periostea, measured and analyzed by immunofluorescence staining and confocal microscopy. Pearson correlation analysis revealed a significant association between skeletal nerve densities and trabecular bone volume/total volume ratios (distal femur; R2 = 0.82, p < 0.05, proximal tibia; R2 = 0.59, p = 0.07) in the exercise group; while in the non-exercise group no significant correlation was found (distal femur; R2 = 0.10, p = 0.54, proximal tibia; R2 = 0.12, p = 0.51). Analysis of archival microarray database confirmed that aerobic exercise training changed the microRNA profiles in the mice femora. The differentially expressed microRNAs reinforce the role of aerobic exercise training in the osteogenic and neurogenic potential of femora and tibiae. In conclusion, 8-weeks of aerobic exercise training positively regulate bone metabolism, an effect that paralleled a significant increase in skeletal nerve fiber density. These findings suggest that aerobic exercise training may have dual utility, both as a direct stimulator of bone remodeling and a positive regulator of skeletal nerve regeneration.

Sclerostin Influences Exercise-Induced Adaptations in Body Composition and White Adipose Tissue Morphology in Male Mice

“…Given sclerostin is a potent inhibitor of bone formation, ( 37 ) we next examined whole‐body bone mineral properties and tibial microarchitecture, a bone region known to demonstrate exercise‐induced responses as a result of increased mechanical loading. ( 38 ) Whole‐body in vivo change in BMC was not influenced by exercise training (F = 2.6, p = 0.1) or sclerostin treatment (F = 0.3, p = 0.6) and there was no exercise*sclerostin interaction (F = 0.4, p = 0.6) (Fig. 4 A ).…”

Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice

“…Given sclerostin is a potent inhibitor of bone formation [30], we next examined whole body bone mineral properties and tibial microarchitecture, a bone region known to demonstrate exercise induced responses as a result of increased mechanical loading (e.g., [31]). Whole body in vivo change in BMC was not influenced by exercise training (p = 0.1) or sclerostin injection (p = 0.6) and there was no exercise*injection interaction (p = 0.6) (Figure 3a).…”

Exercise for osteoporosis: A literature review of pathology and mechanism

“…Few research has been done so far on the impact of circRNAs on bone during exercise, however, to understand their purpose, further research is needed to elaborate on their effects. Lee et al (85) found that improvements in trabecular bone microarchitecture in middle-aged mice were directly associated with increased skeletal nerves after aerobic exercise training. And the expression of seven upstream osteogeneses and neuroplasticity non-coding RNAs, including miR-491-3p, miR-470-5p, let-7a-5p, miR-137-3p, miR-130a3p, and miR-29b-3p, were upregulated after 8 weeks of treadmill activity training.…”