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Characterization of the developing lacuno-canalicular network during fracture repair

Characterization of the developing lacuno-canalicular network during fracture repair
Characterization of the developing lacuno-canalicular network during fracture repair
Fracture repair is a normal physiological response to bone injury. During the process of bony callus formation, a lacuno-canalicular network (LCN) is formed de novo that evolves with callus remodeling. Our aim was the longitudinal assessment of the development and evolution of the LCN during fracture repair. To this end, 45 adult wild type C57BL/6 mice underwent closed tibial fracture surgery. Fractured and intact contralateral tibiae were harvested after 2, 3, and 6 weeks of bone healing (n = 15/group). High-resolution micro-computed tomography (μCT) and deconvolution microscopy (DV) approaches were applied to quantify lacunar number density from the calluses and intact bone. On histological sections, Goldner's trichrome staining was used to assess lacunar occupancy, fluorescein isothiocyanate staining to visualize the canalicular network, and TUNEL staining to examine osteocyte apoptosis. Analysis of μCT scans showed progressive decreases in mean lacuna volume over time (−27% 2–3 weeks, −13% 3–6 weeks). Lacunar number density increased considerably between 2 and 3 weeks (+156%). Correlation analysis was performed, showing a positive linear relationship between canalicular number density and trabecular thickness (R2 = 0.56, p < 0.001) and an inverse relationship between mean lacuna volume and trabecular thickness (R2 = 0.57, p < 0.001). Histology showed increases in canalicular number density over time (+22% 2–3 weeks, +51% 3–6 weeks). Lacunar occupancy in new bone of the callus was high (>90%), but the old cortical bone within the fracture site appeared necrotic as it underwent resorption. In conclusion, our data shows a progressive increase in the complexity of the LCN over time during fracture healing and demonstrates that this network is initiated during the early stages of repair. Further studies are needed to address the functional importance of osteocytes in bone healing, particularly in detecting and translating the effects of micromotion in the fracture.
BONE QUALITY, CANALICULI, OSTEOCYTE LACUNAE, LACUNOCANALICULAR NETWORK, FRACTURE REPAIR, MICRO–COMPUTED TOMOGRAPHY
2473-4039
Casanova, Michele
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Schindeler, Aaron
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Peacock, Lauren
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Lee, Lucinda
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Schneider, Philipp
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Little, David G
feeb48ad-ad99-418d-a3bf-04c151e202b9
Müller, Ralph
c83a3760-2e7b-4e16-a8fe-1d9c538d7076
Casanova, Michele
6fece42d-9268-4e0f-9c14-1b1b4d74961e
Schindeler, Aaron
8d1eff15-dc0d-4fd7-ba28-06c2d41cd5cb
Peacock, Lauren
01253127-9f7e-416a-865d-81726d916ea5
Lee, Lucinda
5a6f7893-b8f4-452d-9bf1-2f0af6a9a349
Schneider, Philipp
a810f925-4808-44e4-8a4a-a51586f9d7ad
Little, David G
feeb48ad-ad99-418d-a3bf-04c151e202b9
Müller, Ralph
c83a3760-2e7b-4e16-a8fe-1d9c538d7076

Casanova, Michele, Schindeler, Aaron, Peacock, Lauren, Lee, Lucinda, Schneider, Philipp, Little, David G and Müller, Ralph (2021) Characterization of the developing lacuno-canalicular network during fracture repair. JBMR Plus, 5 (9), [e10525]. (doi:10.1002/jbm4.10525).

Record type: Article

Abstract

Fracture repair is a normal physiological response to bone injury. During the process of bony callus formation, a lacuno-canalicular network (LCN) is formed de novo that evolves with callus remodeling. Our aim was the longitudinal assessment of the development and evolution of the LCN during fracture repair. To this end, 45 adult wild type C57BL/6 mice underwent closed tibial fracture surgery. Fractured and intact contralateral tibiae were harvested after 2, 3, and 6 weeks of bone healing (n = 15/group). High-resolution micro-computed tomography (μCT) and deconvolution microscopy (DV) approaches were applied to quantify lacunar number density from the calluses and intact bone. On histological sections, Goldner's trichrome staining was used to assess lacunar occupancy, fluorescein isothiocyanate staining to visualize the canalicular network, and TUNEL staining to examine osteocyte apoptosis. Analysis of μCT scans showed progressive decreases in mean lacuna volume over time (−27% 2–3 weeks, −13% 3–6 weeks). Lacunar number density increased considerably between 2 and 3 weeks (+156%). Correlation analysis was performed, showing a positive linear relationship between canalicular number density and trabecular thickness (R2 = 0.56, p < 0.001) and an inverse relationship between mean lacuna volume and trabecular thickness (R2 = 0.57, p < 0.001). Histology showed increases in canalicular number density over time (+22% 2–3 weeks, +51% 3–6 weeks). Lacunar occupancy in new bone of the callus was high (>90%), but the old cortical bone within the fracture site appeared necrotic as it underwent resorption. In conclusion, our data shows a progressive increase in the complexity of the LCN over time during fracture healing and demonstrates that this network is initiated during the early stages of repair. Further studies are needed to address the functional importance of osteocytes in bone healing, particularly in detecting and translating the effects of micromotion in the fracture.

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Accepted/In Press date: 17 June 2021
e-pub ahead of print date: 23 June 2021
Keywords: BONE QUALITY, CANALICULI, OSTEOCYTE LACUNAE, LACUNOCANALICULAR NETWORK, FRACTURE REPAIR, MICRO–COMPUTED TOMOGRAPHY

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Local EPrints ID: 450013
URI: http://eprints.soton.ac.uk/id/eprint/450013
ISSN: 2473-4039
PURE UUID: 0cfc2469-dd45-42df-88a4-dea49438e66e
ORCID for Philipp Schneider: ORCID iD orcid.org/0000-0001-7499-3576

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Date deposited: 05 Jul 2021 16:30
Last modified: 26 Nov 2021 03:01

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Contributors

Author: Michele Casanova
Author: Aaron Schindeler
Author: Lauren Peacock
Author: Lucinda Lee
Author: David G Little
Author: Ralph Müller

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