Neurovascular Interaction and Exercise Training for Bone Regeneration

The nervous and vascular systems are widely distributed in the skeletal system and play an important role in bone metabolism and bone formation, respectively. Their independent impact on the skeletal system has received keen attention in bone-related research over the decade. However, the mechanism of neurovascular coupling during physiological bone remodeling and regeneration has recently been highlighted, considering the importance of spatial relationships between bone-associated skeletal nerves and blood vessels. In addition, the positive effect of exercise on the bones has been continuously emphasized, as evident by the improved number and function of skeletal nerves and blood vessels following exercise training. Skeletal nerve-vascular crosstalk and exercise training are essential for bone development and regeneration, respectively; however, the effect of exercise on neurovascular interactions has not yet been studied. This review aims to summarize the regulatory roles of the nerves and blood vessels in bone metabolism and regeneration and to highlight a combination of potential cellular processes of neurogenesis and angiogenesis in bone regeneration. Moreover, given the significance of the spatial relationship between nerves and blood vessels in bones and the role of exercise training, this review aims to discuss the potential physiological neurovascular coupling that occurs following exercise and physical activity.