Staines, K.A., Javaheri, B., Hohenstein, P. et al. (7 more authors) (2017) Hypomorphic conditional deletion of E11/podoplanin reveals a pivotal role in osteocyte dendrite elongation. Journal of Cellular Physiology, 232 (11). pp. 3006-3019. ISSN 0021-9541
Abstract
The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpnflox/flox (cKO) mice and their Pdpnflox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (P < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (P < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (P < 0.001) and length (P < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (P < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodelling, this highlights an essential role for Pdpn in bone homeostasis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Osteocytes; E11; osteocalcin; osteoblasts; dendrite |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 May 2017 15:11 |
Last Modified: | 28 Jul 2023 14:54 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jcp.25999 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117083 |