Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling
Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling
BACKGROUND: Different pathologies, affecting the skeletal system, were reported to display altered bone and/or cartilage innervation profiles leading to the deregulation of the tissue homeostasis. 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.
RESULTS: Here we show that sensory neurons outgrowth induced by the bone resorbing cells-osteoclasts-is 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.
CONCLUSIONS: 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.
Bone pain, Epidermal growth factor receptor (EGFR/ErbB2) signaling, Extracellular vesicles, Neuronal electrophysiology, Osteoclast secretome, Sensory neurons sprouting
127
Neto, Estrela
c60aa578-7615-4348-ba4b-4fdb30839c23
Leitão, Luís
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Mateus, José C
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Sousa, Daniela M
c534ef67-3d20-4b0b-8cf5-52e85dc493ef
Alves, Cecília J
b6b3af8a-2cc4-4b13-b34e-77efffa72707
Aroso, Miguel
dc58235c-4e3e-42b8-a4aa-2542fe456185
Monteiro, Ana C
89ee3a13-f7da-409f-a59c-bab0c108cc22
Conceição, Francisco
3d75a0e1-e6d7-464c-8efd-55666d44b885
Oreffo, Richard O C
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Aguiar, Paulo
6ba09608-61c4-48e6-a72e-a94dbdaf98ee
Lamghari, Meriem
921008b5-f9bb-4591-a83d-20eaa712207c
14 August 2022
Neto, Estrela
c60aa578-7615-4348-ba4b-4fdb30839c23
Leitão, Luís
7fa05f9c-ca39-4e7c-ac1a-4fed4362be75
Mateus, José C
9b41a7a4-c769-4d47-a1b4-0265c0cf04f9
Sousa, Daniela M
c534ef67-3d20-4b0b-8cf5-52e85dc493ef
Alves, Cecília J
b6b3af8a-2cc4-4b13-b34e-77efffa72707
Aroso, Miguel
dc58235c-4e3e-42b8-a4aa-2542fe456185
Monteiro, Ana C
89ee3a13-f7da-409f-a59c-bab0c108cc22
Conceição, Francisco
3d75a0e1-e6d7-464c-8efd-55666d44b885
Oreffo, Richard O C
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Aguiar, Paulo
6ba09608-61c4-48e6-a72e-a94dbdaf98ee
Lamghari, Meriem
921008b5-f9bb-4591-a83d-20eaa712207c
Neto, Estrela, Leitão, Luís, Mateus, José C, Sousa, Daniela M, Alves, Cecília J, Aroso, Miguel, Monteiro, Ana C, Conceição, Francisco, Oreffo, Richard O C, West, Jonathan, Aguiar, Paulo and Lamghari, Meriem
(2022)
Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling.
Cell & bioscience, 12 (1), , [127].
(doi:10.1186/s13578-022-00864-w).
Abstract
BACKGROUND: Different pathologies, affecting the skeletal system, were reported to display altered bone and/or cartilage innervation profiles leading to the deregulation of the tissue homeostasis. 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.
RESULTS: Here we show that sensory neurons outgrowth induced by the bone resorbing cells-osteoclasts-is 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.
CONCLUSIONS: 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.
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Published date: 14 August 2022
Additional Information:
Funding Information:
This work received funding from the FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project SproutOC: POCI-01-0145-FEDER-030158, PTDC/MED-PAT/30158/2017. EN is supported by FCT (CEECIND/01760/2018). LL, JCM, FC and DMS are recipients of SFRH/BD/109686/2015, PD/BD/135491/2018, SFRH/BD/128771/2017 and SFRH/BPD/115341/2016 fellowships, respectively. The authors acknowledge the support of the i3S Scientific Platforms BioSciences Screening, Bioimaging, and Histology and Electron Microscopy, members of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122). Transmission Electron microscopy assay was conducted by of Rui Fernandes.
Publisher Copyright:
© 2022, The Author(s).
Keywords:
Bone pain, Epidermal growth factor receptor (EGFR/ErbB2) signaling, Extracellular vesicles, Neuronal electrophysiology, Osteoclast secretome, Sensory neurons sprouting
Identifiers
Local EPrints ID: 468654
URI: http://eprints.soton.ac.uk/id/eprint/468654
ISSN: 2045-3701
PURE UUID: 2e40d7bf-cb8c-4644-9cd3-e845b0f6d7af
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Date deposited: 19 Aug 2022 16:43
Last modified: 06 Jun 2024 01:50
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Contributors
Author:
Estrela Neto
Author:
Luís Leitão
Author:
José C Mateus
Author:
Daniela M Sousa
Author:
Cecília J Alves
Author:
Miguel Aroso
Author:
Ana C Monteiro
Author:
Francisco Conceição
Author:
Paulo Aguiar
Author:
Meriem Lamghari
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