2019
DOI: 10.1038/s41467-019-13476-9
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Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice

Abstract: Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerve… Show more

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Cited by 97 publications
(138 citation statements)
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“…BMSC are known to promote axon growth through the secretion of neurotrophins (Cantinieaux et al, 2013; Gu et al, 2012, 2010) and osteoclasts where described to induce nerve outgrowth through netrin-1 action (Ni et al, 2019; Zhu et al, 2019). To assess if the osteoclast secretome observed effect follow similar mechanisms, we measured in the conditioned medium the levels of NGF, BDNF, NT-3, NT-4/5 and netrin-1, by enzyme-linked immunosorbent assay (ELISA).…”
Section: Resultsmentioning
confidence: 99%
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“…BMSC are known to promote axon growth through the secretion of neurotrophins (Cantinieaux et al, 2013; Gu et al, 2012, 2010) and osteoclasts where described to induce nerve outgrowth through netrin-1 action (Ni et al, 2019; Zhu et al, 2019). To assess if the osteoclast secretome observed effect follow similar mechanisms, we measured in the conditioned medium the levels of NGF, BDNF, NT-3, NT-4/5 and netrin-1, by enzyme-linked immunosorbent assay (ELISA).…”
Section: Resultsmentioning
confidence: 99%
“…Different studies point to a parallel between osteoclast activity and sensory neurons outgrowth in physiological and pathological conditions (Cheung et al, 2009; Clarke, 2008; Gajda et al, 2005; Kumar et al, 2011; Mediati et al, 2014; Nagae et al, 2006; Ni et al, 2019; Reddy et al, 1999; Riminucci et al, 2003; Sisask et al, 1996, 2013; Zhu et al, 2019). Several reports have described that during embryonic long bone development, osteoclasts are found in the process of endochondral ossification, degrading the newly formed trabecular bone, creating the bone marrow space (Clarke, 2008).…”
Section: Discussionmentioning
confidence: 99%
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