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Sensory innervation induced by osteoblast-derived netrin-4 attenuates bone loss in aged mice

GSE317225 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2026/01/27 Platform GPL13112
Summary
The sensory denervation has a causal role in bone loss. The mechanism of bone cells regulation of sensory nerve wiring and sprouting for maintaining bone homeostasis remains unclear. Here we found that netrin-4, secreted by osteoblasts, facilitates the sprouting of sensory nerves through the DCC receptor and plays a regulatory role in bone formation. Decreased bone formation is coupled with reduced sensory innervation in aged mice and ablation of sensory nerves recapitulates this phenotype. Both mice and human data reveal that netrin-4 is positively correlated with bone volume, which expression was not affected by ablation of sensory nerves in mice. The sensory sprouting and bone formation are inhibited by siDCC, a netrin-4 receptor antagonist, in vivo and in vitro. Specifically, knockout of the netrin4 gene in the osteoblastic cells significantly reduces both sensory innervation and bone volume in adult mice. Thus, we show that sensory innervation induced by osteoblast-derived netrin-4 preserve bone homeostasis and attenuates bone loss in aged mice.
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Also filed as BioProject PRJNA1406306 and SRA study SRP665365. Searching any of these in the dataset finder brings you back here.

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