Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.

ABSTRACT: Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α⁺ nerve fibers, which sense the inflammatory cue with PGE₂ receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of E

SUBMITTER: Qiao W 

PROVIDER: S-EPMC8795158 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature