BoneKEy Reports | BoneKEy Watch

Bone mass is regulated by a central IL-1–PSNS–bone axis


Investigating a theory that signals from the central nervous system (CNS) carried by the parasympathetic nervous system (PSNS) via interleukin-1 (IL-1) impact on bone mass accrual, Bajayo et al. report the novel finding that all bones in the skeleton are innervated by the PSNS. Mice in which IL-1 receptor signaling was silenced in the CNS had low bone mass due to increased bone resorption, low levels of acetylcholine (ACh) and much-reduced vesicular ACh transporter expression.

Bone ACh receptors are of the subtype α2ß2nAChR. Experiments with carbamylcholine and nicotine, both cholinergic agonists that are resistant to acetylcholinesterase (AChE), revealed that cholinergic signaling stimulates apoptosis in osteoclasts, so inhibiting bone resorption. Stimulation of the ACh receptor in bone resulted in osteoblast proliferation, an effect that did not change levels of RANKL or osteoprotegerin. This suggests that the effects of cholinergic signaling on osteoclasts and osteoblasts occur independently.

These observations may help explain why patients with disorders such as clinical depression, Alzheimer's and epilepsy often suffer reduced bone mass and an increased risk of osteoporosis.

Editor's comment: This is the first report confirming the existence of a central IL-1–PSNS–bone axis that antagonizes the sympathetic nervous system and inhibits bone resorption. As this axis also affects the immune system, it will be interesting to explore the role of the PSNS as a link between the autonomic nervous system and osteoimmune physiology.

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