Direct effect of sclerostin on the mechanical loading response in bovine bone

Sclerostin is expressed exclusively by mature osteocytes in bone. Our recent findings indicate that sclerostin targets pre-osteocytes/osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo is associated with th...

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Main Authors:	Khalid, Kamarul Ariffin, Kogawa, Masakazu, Wijenayaka, Asiri R, Findlay, David M, Atkins, Gerald J
Format:	Conference or Workshop Item
Language:	English
Published:	2012
Subjects:	QH301 Biology QP Physiology R Medicine (General) RD701 Orthopedics
Online Access:	http://irep.iium.edu.my/66161/ http://irep.iium.edu.my/66161/27/66161%20Direct%20effect%20of%20sclerostin%20on%20the%20mechanical%20loading%20response%20in%20bovine%20bone.PDF

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spelling	iium-661612018-10-04T04:13:10Z http://irep.iium.edu.my/66161/ Direct effect of sclerostin on the mechanical loading response in bovine bone Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J QH301 Biology QP Physiology R Medicine (General) RD701 Orthopedics Sclerostin is expressed exclusively by mature osteocytes in bone. Our recent findings indicate that sclerostin targets pre-osteocytes/osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo is associated with the osteocyte response to mechanical loading/unloading. The aim of this study was to examine the 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 microstrain, 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 a Zetos(TM) bone loading system. Daily measurements of bone 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 with mechanical loading but this was blocked by the addition of sclerostin. Media pH decreased and ionic calcium concentrations increased in the presence of sclerostin. Sclerostin also completely abrogated loading-induced calcium/calcein uptake, together suggesting 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 to mechanical loading. 1. Atkins et al. J Bone Miner Res. 201 1 26(7):1425-36. 2. Wijenayaka et al. PLoS One. 201 1 ;6(10):e25900. 3. Kogawa M. et al. Abstract at this meeting. 2012 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/66161/27/66161%20Direct%20effect%20of%20sclerostin%20on%20the%20mechanical%20loading%20response%20in%20bovine%20bone.PDF Khalid, Kamarul Ariffin and Kogawa, Masakazu and Wijenayaka, Asiri R and Findlay, David M and Atkins, Gerald J (2012) Direct effect of sclerostin on the mechanical loading response in bovine bone. In: 1st Asia Pacific Bone and Mineral Research Meeting and the Australian & New Zealand Bone & Mineral Society 22nd Annual Scientific Meeting, 2 - 5 September 2012, Perth, Australia.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QH301 Biology QP Physiology R Medicine (General) RD701 Orthopedics
spellingShingle	QH301 Biology QP Physiology R Medicine (General) RD701 Orthopedics Khalid, Kamarul Ariffin Kogawa, Masakazu Wijenayaka, Asiri R Findlay, David M Atkins, Gerald J Direct effect of sclerostin on the mechanical loading response in bovine bone
description	Sclerostin is expressed exclusively by mature osteocytes in bone. Our recent findings indicate that sclerostin targets pre-osteocytes/osteocytes to regulate bone mineralisation(1), osteoclast activity(2), and, potentially, osteocytic osteolysis(3). Sclerostin expression in vivo is associated with the osteocyte response to mechanical loading/unloading. The aim of this study was to examine the 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 microstrain, 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 a Zetos(TM) bone loading system. Daily measurements of bone 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 with mechanical loading but this was blocked by the addition of sclerostin. Media pH decreased and ionic calcium concentrations increased in the presence of sclerostin. Sclerostin also completely abrogated loading-induced calcium/calcein uptake, together suggesting 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 to mechanical loading. 1. Atkins et al. J Bone Miner Res. 201 1 26(7):1425-36. 2. Wijenayaka et al. PLoS One. 201 1 ;6(10):e25900. 3. Kogawa M. et al. Abstract at this meeting.
format	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	Direct effect of sclerostin on the mechanical loading response in bovine bone
title_short	Direct effect of sclerostin on the mechanical loading response in bovine bone
title_full	Direct effect of sclerostin on the mechanical loading response in bovine bone
title_fullStr	Direct effect of sclerostin on the mechanical loading response in bovine bone
title_full_unstemmed	Direct effect of sclerostin on the mechanical loading response in bovine bone
title_sort	direct effect of sclerostin on the mechanical loading response in bovine bone
publishDate	2012
url	http://irep.iium.edu.my/66161/ http://irep.iium.edu.my/66161/27/66161%20Direct%20effect%20of%20sclerostin%20on%20the%20mechanical%20loading%20response%20in%20bovine%20bone.PDF
first_indexed	2023-09-18T21:33:53Z
last_indexed	2023-09-18T21:33:53Z
_version_	1777412691137134592

Direct effect of sclerostin on the mechanical loading response in bovine bone

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