Skeletal interoception in bone homeostasis and pain

Accumulating evidence indicates that interoception maintains proper physiological status and orchestrates metabolic homeostasis by regulating feeding behaviors, glucose balance, and lipid metabolism. Continuous skeletal remodeling consumes a tremendous amount of energy to provide skeletal scaffolding, support mus-cle movement, store vital minerals, and maintain a niche for hematopoiesis, which are processes that also contribute to overall metabolic balance. Although skeletal innervation has been described for centuries, recent work has shown that skeletal metabolism is tightly regulated by the nervous system and that skeletal interoception regulates bone homeostasis. Here, we provide a general discussion of interoception and its ef-fects on the skeleton and whole-body metabolism. We also discuss skeletal interoception-mediated regula-tion in the context of pathological conditions and skeletal pain as well as future challenges to our understand-ing of these process and how they can be leveraged for more effective therapy.

Automated summary

Accumulating evidence suggests that interoception plays a crucial role in maintaining physiological status and metabolic balance by regulating feeding behaviors, glucose balance, and lipid metabolism. Recent research has shown that skeletal metabolism is tightly regulated by the nervous system through skeletal interoception, which contributes to bone homeostasis. This article provides an overview of interoception and its effects on the skeleton and whole-body metabolism, as well as discussing its potential applications in pathological conditions, skeletal pain, and future challenges in understanding and utilizing these processes for therapy.