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

• 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/66161/27/66161%20Direct%20effect%20of%20sclerostin%20on%20the%20mechanical%20loading%20response%20in%20bovine%20bone.PDF; http://irep.iium.edu.my/66161/

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.