Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse

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Abstract

Objectives

The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses.

Methods

A total of 30 Mc-III bones were obtained; ten bones were fractured during racing, ten were from the contralateral limb, and ten were from control horses. Each Mc-III bone was divided into a fracture site, condyle, condylar groove, and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13), HtrA1, and sclerostin expression were analyzed.

Results

In the fracture group, microdamage was elevated 38.9% ( sd 2.6) compared with controls. There was no difference in the osteocyte number and the percentage of apoptotic cells between contralateral limb and unraced control; however, there were significantly fewer apoptotic cells in fractured samples (p < 0.02). Immunohistochemistry showed that in deep zones of the fractured samples, sclerostin expression was significantly higher (p < 0.03) than the total number of osteocytes. No increase in cathepsin K, MMP-13, or HtrA1 was present.

Conclusion

There is increased microdamage in Mc-III bones that have fractured during racing. In this study, this is not associated with osteocyte apoptosis or osteocytic osteolysis. The finding of increased sclerostin in the region of the fracture suggests that this protein may be playing a key role in the regulation of bone microdamage during stress adaptation.

Cite this article: N. Hopper, E. Singer, F. Henson. Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse. Bone Joint Res 2018;7:94–102. DOI: 10.1302/2046-3758.71.BJR-2016-0202.R4.

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Most cited references 38

Record: found
Abstract: found
Article: not found

NIH Image to ImageJ: 25 years of image analysis.

Lynda C. Schneider, Wayne S Rasband (2013)

For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.

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Record: found
Abstract: found
Article: not found

Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo.

O Verborgt, G J Gibson, M B Schaffler (2000)

As a result of fatigue, bone sustains microdamage, which is then repaired by bone-remodeling processes. How osteoclastic activity is targeted at the removal of microdamaged regions of bone matrix is unknown. In the current studies, we tested the hypothesis that changes in osteocyte integrity, through the initiation of regulated cell death (apoptosis), are associated with fatigue-related microdamage and bone resorption. Ulnae of adult rats were fatigue-loaded to produce a known degree of matrix damage. Osteocyte integrity was then assessed histomorphometrically from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL)-stained sections to detect cells undergoing DNA fragmentation associated with apoptosis; toluidine blue-stained sections were used for secondary morphological confirmation. Ten days after loading, large numbers of TUNEL-positive osteocytes were found in bone surrounding microcracks and in bone surrounding intracortical resorption spaces (approximately 300% increases over controls, p < 0.005). TUNEL labeling in loaded ulnae at sites distant from microcracks or resorption foci did not differ from that in control bone. Osteocytes in toluidine blue-stained sections showed equivalent trends to TUNEL-stained sections, with significant increases in pyknotic nuclei and empty lacunae associated with microcracks and intracortical resorption spaces. TUNEL-positive osteocytes were observed around bone microdamage by 1 day after loading (p < 0.01 relative to baseline), and their number remained elevated throughout the entire experimental period. Increases in empty lacunae and decreases in normal osteocyte numbers were observed over time as well. These studies show that (1) osteocyte apoptosis is induced by bone fatigue, (2) this apoptosis is localized to regions of bone that contain microcracks, and (3) osteoclastic resorption after fatigue also coincides with regions of osteocyte apoptosis. The strong associations between microdamage, osteocyte apoptosis, and subsequent bone remodeling support the hypothesis that osteocyte apoptosis provides a key part of the activation or signaling mechanisms by which osteoclasts target bone for removal after fatigue-induced matrix injury.

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Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone.

Xiaolin Tu, Jesús Delgado-Calle, Keith Condon … (2015)

Osteocytes, >90% of the cells in bone, lie embedded within the mineralized matrix and coordinate osteoclast and osteoblast activity on bone surfaces by mechanisms still unclear. Bone anabolic stimuli activate Wnt signaling, and human mutations of components along this pathway underscore its crucial role in bone accrual and maintenance. However, the cell responsible for orchestrating Wnt anabolic actions has remained elusive. We show herein that activation of canonical Wnt signaling exclusively in osteocytes [dominant active (da)βcat(Ot) mice] induces bone anabolism and triggers Notch signaling without affecting survival. These features contrast with those of mice expressing the same daß-catenin in osteoblasts, which exhibit decreased resorption and perinatal death from leukemia. daßcat(Ot) mice exhibit increased bone mineral density in the axial and appendicular skeleton, and marked increase in bone volume in cancellous/trabecular and cortical compartments compared with littermate controls. daßcat(Ot) mice display increased resorption and formation markers, high number of osteoclasts and osteoblasts in cancellous and cortical bone, increased bone matrix production, and markedly elevated periosteal bone formation rate. Wnt and Notch signaling target genes, osteoblast and osteocyte markers, and proosteoclastogenic and antiosteoclastogenic cytokines are elevated in bones of daßcat(Ot) mice. Further, the increase in RANKL depends on Sost/sclerostin. Thus, activation of osteocytic β-catenin signaling increases both osteoclasts and osteoblasts, leading to bone gain, and is sufficient to activate the Notch pathway. These findings demonstrate disparate outcomes of β-catenin activation in osteocytes versus osteoblasts and identify osteocytes as central target cells of the anabolic actions of canonical Wnt/β-catenin signaling in bone.

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Author and article information

Contributors

N. Hopper: Role: Research Associate

E. Singer: Role: Senior Lecturer in Equine Orthopaedics

F. Henson: Role: Senior Lecturer in Equine Surgery

Journal

Journal ID (nlm-ta): Bone Joint Res

Title: Bone & Joint Research

ISSN (Electronic): 2046-3758

Publication date Collection: January 2018

Publication date (Electronic): 8 February 2018

Volume: 7

Issue: 1

Pages: 94-102

Affiliations

[1 ]Department of Surgery, University of Cambridge

[2 ]Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, School of Veterinary Medicine, Leahurst, Chester High Road, Neston CH64 6SW, UK

[3 ]Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK and Division of Trauma and Orthopaedic Surgery, University of Cambridge, Hills Road, Cambridge BC2 0QQ, UK

Author notes

[*]N. Hopper; email: niina.hopper@ 123456gmail.com

Article

Publisher ID: 10.1302_2046-3758.71.BJR-2016-0202.R4

DOI: 10.1302/2046-3758.71.BJR-2016-0202.R4

PMC ID: 5805827

PubMed ID: 29363519

SO-VID: 28e40590-c565-4f36-8f49-49de24b1c822

License:

This is an open-access article distributed under the terms of the Creative Commons Attributions licence (CC-BY-NC), which permits unrestricted use, distribution, and reproduction in any medium, but not for commercial gain, provided the original author and source are credited.

Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse

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Abstract

Objectives

Methods

Results

Conclusion

Related collections

Fracture and Structural Integrity

Most cited references 38

NIH Image to ImageJ: 25 years of image analysis.

Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo.

Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone.

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