Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration
Sclerostin is expressed almost exclusively by mature osteocytes in bone. Recent findings from this lab indicate that sclerostin targets pre-osteocytes and osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo...
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Australian Health and Medical Research Council
2012
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my.iium.irep.298382018-10-05T00:23:27Z http://irep.iium.edu.my/29838/ Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J QH301 Biology RD701 Orthopedics Sclerostin is expressed almost exclusively by mature osteocytes in bone. Recent findings from this lab indicate that sclerostin targets pre-osteocytes and osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo is associated with the response of osteocytes to mechanical loading and unloading. The aim of this study was to examine the direct effects of sclerostin on loading-induced bone growth ex vivo. For this, 10x5mm bovine sternum trabecular bone cores were perfused with osteogenic media at 37°C for up to 3 weeks in individual bone culture chambers. The cores were divided into 3 groups; a) mechanically loaded (300 cycles, 4000 µstrain, 1 Hz/day), b) identical loading regime with continuous perfusion of 50 ng/ml recombinant human sclerostin and c) unloaded controls. Loading was accomplished using the Zetos™ long-term bone organ culture and piezo-electric bone loading system. Daily measurements of the bone core stiffness, media pH and ionic calcium concentrations were made. Histomorphometric assessment, including fluorochrome labelling analysis, was made at the end of the experiment. Bone stiffness increased greatly with mechanical loading but this was attenuated significantly with the addition of sclerostin. The pH of the media after 24 hours decreased and ionic calcium concentrations increased in the presence of sclerostin when compared to mechanical loading alone. Sclerostin also completely abrogated loading-induced calcium/calcein uptake by the bone cores. Together, the results suggest that an osteocyte/osteoclast response to sclerostin was responsible for these effects. Our results are the first direct evidence for a negative effect of sclerostin on the anabolic response of bone to mechanical loading. Australian Health and Medical Research Council 2012 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/29838/17/29838%20-abstract.PDF application/pdf en http://irep.iium.edu.my/29838/1/AHMRC_2012_Poster_Kamarul_Final.pdf application/pdf en http://irep.iium.edu.my/29838/2/AHMRC_2012_Kamarul_Final.pdf Khalid, Kamarul Ariffin and Kogawa, Masakazu and Wijenayaka, Asiri R and Findlay, David M and Atkins, Gerald J (2012) Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration. In: 6th Australian Health and Medical Research Congress 2012, 25th - 28th November 2012, Adelaide, South Australia, Australia. (Unpublished) |
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QH301 Biology RD701 Orthopedics Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
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Sclerostin is expressed almost exclusively by mature osteocytes in bone. Recent findings from this lab indicate that sclerostin targets pre-osteocytes and osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo is associated with the response of osteocytes to mechanical loading and unloading.
The aim of this study was to examine the direct effects of sclerostin on loading-induced bone growth ex vivo. For this, 10x5mm bovine sternum trabecular bone cores were perfused with osteogenic media at 37°C for up to 3 weeks in individual bone culture chambers. The cores were divided into 3 groups; a) mechanically loaded (300 cycles, 4000 µstrain, 1 Hz/day), b) identical loading regime with continuous perfusion of 50 ng/ml recombinant human sclerostin and c) unloaded controls. Loading was accomplished using the Zetos™ long-term bone organ culture and piezo-electric bone loading system. Daily measurements of the bone core stiffness, media pH and ionic calcium concentrations were made. Histomorphometric assessment, including fluorochrome labelling analysis, was made at the end of the experiment.
Bone stiffness increased greatly with mechanical loading but this was attenuated significantly with the addition of sclerostin. The pH of the media after 24 hours decreased and ionic calcium concentrations increased in the presence of sclerostin when compared to mechanical loading alone. Sclerostin also completely abrogated loading-induced calcium/calcein uptake by the bone cores.
Together, the results suggest that an osteocyte/osteoclast response to sclerostin was responsible for these effects. Our results are the first direct evidence for a negative effect of sclerostin on the anabolic response of bone to mechanical loading. |
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Conference or Workshop Item |
author |
Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J |
author_facet |
Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J |
author_sort |
Khalid, Kamarul Ariffin |
title |
Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
title_short |
Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
title_full |
Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
title_fullStr |
Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
title_full_unstemmed |
Mechanical loading response in trabecular bone is abrogated by sclerostin - A direct demonstration |
title_sort |
mechanical loading response in trabecular bone is abrogated by sclerostin - a direct demonstration |
publisher |
Australian Health and Medical Research Council |
publishDate |
2012 |
url |
http://irep.iium.edu.my/29838/17/29838%20-abstract.PDF http://irep.iium.edu.my/29838/1/AHMRC_2012_Poster_Kamarul_Final.pdf http://irep.iium.edu.my/29838/2/AHMRC_2012_Kamarul_Final.pdf http://irep.iium.edu.my/29838/ |
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