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The patterning of peripheral innervation is achieved through the tissue-specific expression of attractive or repulsive axonal guidance cues in specific space and time frames. During the last decade, emerging findings attributed to the extracellular vesicles (EV) trading a central role in peripheral tissue innervation. However, to date, the contribution of EV in controlling bone innervation is totally unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here we show that sensory neurons outgrowth induced by the bone resorbing cells\u2014osteoclasts\u2014is promoted by osteoclast-derived EV. The EV induced axonal growth is achieved by targeting epidermal growth factor receptor (EGFR)\/ErbB2 signaling\/protein kinase C phosphorylation in sensory neurons. In addition, our data also indicate that osteoclasts promote sensory neurons electrophysiological activity reflecting a possible pathway in nerve sensitization in the bone microenvironment, however this effect is EV independent.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overall, these results identify a new mechanism of sensory bone innervation regulation and shed the light on the role of osteoclast-derived EV in shaping\/guiding bone sensory innervation. These findings provide opportunities for exploitation of osteoclast-derived EV based strategies to prevent and\/or mitigate pathological uncontrolled bone innervation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13578-022-00864-w","type":"journal-article","created":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T07:02:22Z","timestamp":1660460542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-2292","authenticated-orcid":false,"given":"Estrela","family":"Neto","sequence":"first","affiliation":[]},{"given":"Lu\u00eds","family":"Leit\u00e3o","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 C.","family":"Mateus","sequence":"additional","affiliation":[]},{"given":"Daniela M.","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Cec\u00edlia J.","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Aroso","sequence":"additional","affiliation":[]},{"given":"Ana C.","family":"Monteiro","sequence":"additional","affiliation":[]},{"given":"Francisco","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[]},{"given":"Richard O. 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