Sclerostin attenuates the mechanical loading response in trabecular bone

Osteocytes play a major role in normal bone maintenance and have recently been implicated in a number of conditions that affect bone. Sclerostin is an osteocyte secreted protein, deficiency of which was found to be causative of the high bone mass phenotype in patients with sclerosteosis and van Buch...

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Main Authors:	Khalid, Kamarul Ariffin, Kogawa, Masakagi, Findlay, David M, Atkins, Gerald J
Format:	Conference or Workshop Item
Language:	English
Published:	2012
Subjects:	QH301 Biology R Medicine (General) RD701 Orthopedics
Online Access:	http://irep.iium.edu.my/66314/ http://irep.iium.edu.my/66314/11/66314%20abstract.PDF

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spelling	iium-663142018-10-08T02:48:40Z http://irep.iium.edu.my/66314/ Sclerostin attenuates the mechanical loading response in trabecular bone Khalid, Kamarul Ariffin Kogawa, Masakagi Findlay, David M Atkins, Gerald J QH301 Biology R Medicine (General) RD701 Orthopedics Osteocytes play a major role in normal bone maintenance and have recently been implicated in a number of conditions that affect bone. Sclerostin is an osteocyte secreted protein, deficiency of which was found to be causative of the high bone mass phenotype in patients with sclerosteosis and van Buchem's disease. Mechanical loading of bone within the anabolic range decreases osteocyte sclerostin expression. An anti-sclerostin antibody, currently undergoing clinical trials, has been developed as a bone anabolic agent. Recent evidence from in vitro and in vivo experiments shows that osteocytes, via sclerostin, downregulate osteoblastogenesis (anti-anabolic) and potentiate osteoclastogenesis procatabolic) activity. PURPOSE OF STUDY In this study, the interaction between sclerostin and mechanical loading was investigated in bovine trabecular bone cores cultured ex vivo. METHODS Using a novel bone organ culture system, fresh bovine trabecular bone cores were cultured for up to 3 weeks. The cores were divided into 3 groups; A (loaded, using the Zetos™ piezoelectric loading system), which were subjected to daily mechanical loading (300 cycles of 4,000 μstrain at 1 Hz), B (loaded + sclerostin), which had an identical loading regime and were perfused continuously with 50 ng/ml recombinant human sclerostin, and C (unloaded), which were not loaded and were perfused with medium in the absence of sclerostin. Daily measurements of stiffness, pH and ionic calcium were made. Calcein was introduced both one week and one day before the experiment was ended. RESULTS The stiffness of the cores increased in response to mechanical loading in A. Samples in B had a significantly lower response to mechanical loading. The pH of medium from both B and C was significantly lower than that from A. The ionic calcium concentration present in the culture media after 24 hours was higher in B than in A. Calcein uptake in B was also observed to be less than in A. CONCLUSIONS This is the first direct evidence that sclerostin blunts the anabolic effect of mechanical loading via reduced bone formation, which is in agreement with current in vitro and in vivo published work. The ex vivo culture of trabecular bone appears to be an ideal model for the demonstration of direct effects of bone acting agents in large mammals. 2012 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/66314/11/66314%20abstract.PDF Khalid, Kamarul Ariffin and Kogawa, Masakagi and Findlay, David M and Atkins, Gerald J (2012) Sclerostin attenuates the mechanical loading response in trabecular bone. In: Australian Orthopaedic Association - South Australian Branch Annual Scientific Meeting, 10th August 2012, Adelaide, South Australia, 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 R Medicine (General) RD701 Orthopedics
spellingShingle	QH301 Biology R Medicine (General) RD701 Orthopedics Khalid, Kamarul Ariffin Kogawa, Masakagi Findlay, David M Atkins, Gerald J Sclerostin attenuates the mechanical loading response in trabecular bone
description	Osteocytes play a major role in normal bone maintenance and have recently been implicated in a number of conditions that affect bone. Sclerostin is an osteocyte secreted protein, deficiency of which was found to be causative of the high bone mass phenotype in patients with sclerosteosis and van Buchem's disease. Mechanical loading of bone within the anabolic range decreases osteocyte sclerostin expression. An anti-sclerostin antibody, currently undergoing clinical trials, has been developed as a bone anabolic agent. Recent evidence from in vitro and in vivo experiments shows that osteocytes, via sclerostin, downregulate osteoblastogenesis (anti-anabolic) and potentiate osteoclastogenesis procatabolic) activity. PURPOSE OF STUDY In this study, the interaction between sclerostin and mechanical loading was investigated in bovine trabecular bone cores cultured ex vivo. METHODS Using a novel bone organ culture system, fresh bovine trabecular bone cores were cultured for up to 3 weeks. The cores were divided into 3 groups; A (loaded, using the Zetos™ piezoelectric loading system), which were subjected to daily mechanical loading (300 cycles of 4,000 μstrain at 1 Hz), B (loaded + sclerostin), which had an identical loading regime and were perfused continuously with 50 ng/ml recombinant human sclerostin, and C (unloaded), which were not loaded and were perfused with medium in the absence of sclerostin. Daily measurements of stiffness, pH and ionic calcium were made. Calcein was introduced both one week and one day before the experiment was ended. RESULTS The stiffness of the cores increased in response to mechanical loading in A. Samples in B had a significantly lower response to mechanical loading. The pH of medium from both B and C was significantly lower than that from A. The ionic calcium concentration present in the culture media after 24 hours was higher in B than in A. Calcein uptake in B was also observed to be less than in A. CONCLUSIONS This is the first direct evidence that sclerostin blunts the anabolic effect of mechanical loading via reduced bone formation, which is in agreement with current in vitro and in vivo published work. The ex vivo culture of trabecular bone appears to be an ideal model for the demonstration of direct effects of bone acting agents in large mammals.
format	Conference or Workshop Item
author	Khalid, Kamarul Ariffin Kogawa, Masakagi Findlay, David M Atkins, Gerald J
author_facet	Khalid, Kamarul Ariffin Kogawa, Masakagi Findlay, David M Atkins, Gerald J
author_sort	Khalid, Kamarul Ariffin
title	Sclerostin attenuates the mechanical loading response in trabecular bone
title_short	Sclerostin attenuates the mechanical loading response in trabecular bone
title_full	Sclerostin attenuates the mechanical loading response in trabecular bone
title_fullStr	Sclerostin attenuates the mechanical loading response in trabecular bone
title_full_unstemmed	Sclerostin attenuates the mechanical loading response in trabecular bone
title_sort	sclerostin attenuates the mechanical loading response in trabecular bone
publishDate	2012
url	http://irep.iium.edu.my/66314/ http://irep.iium.edu.my/66314/11/66314%20abstract.PDF
first_indexed	2023-09-18T21:34:08Z
last_indexed	2023-09-18T21:34:08Z
_version_	1777412706767208448

Sclerostin attenuates the mechanical loading response in trabecular bone

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