Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered

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Moustafa, A.^1,2; Sugiyama, T.^1,3; Prasad, J.⁴; Zaman, G.¹; Gross, T. S.⁴; Lanyon, L. E.^1,3; Price, J. S.^1,3

Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered

Osteoporos Int. April 2012;23(4):1225-1234

©2011 The Author(s)

Affiliations

¹Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, London, UK

²Department of Surgery, Faculty of Veterinary Medicine, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt

³School of Veterinary Sciences, University of Bristol, Langford, UK

⁴Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, USA
Abstract and keywords

Summary: Osteocyte sclerostin is regulated by loading and disuse in mouse tibiae but is more closely related to subsequent local osteogenesis than the peak strains engendered.

Introduction: The purpose of this study was to assess the relationship between loading-related change in osteocyte sclerostin expression, local strain magnitude, and local bone modeling/remodeling.

Methods: The right tibiae of 19-week-old female C57BL/6 mice were subjected to non-invasive, dynamic axial loading and/or to sciatic neurectomy-induced disuse. The sclerostin status of osteocytes was evaluated immunohistochemically, changes in bone mass by micro-computed tomography, new bone formation by histomorphometry, and loading-induced strain by strain gauges and finite element analysis.

Results: In cortical bone of the tibial shaft, loading engendered strains of similar peak magnitude proximally and distally. Proximally, sclerostin-positive osteocytes decreased and new bone formation increased. Distally, there was neither decrease in sclerostin-positive osteocytes nor increased osteogenesis. In trabecular bone of the proximal secondary spongiosa, loading decreased sclerostin-positive osteocytes and increased bone volume. Neither occurred in the primary spongiosa. Disuse increased sclerostin-positive osteocytes and decreased bone volume at all four sites. Loading reversed this sclerostin upregulation to a level below baseline in the proximal cortex and secondary spongiosa.

Conclusion: Loading-related sclerostin downregulation in osteocytes of the mouse tibia is associated preferentially with regions where new bone formation is stimulated rather than where high peak strains are engendered. The mechanisms involved remain unclear, but could relate to peak surface strains not accurately reflecting the strain-related osteogenic stimulus or that sclerostin regulation occurs after sufficient signal processing to distinguish between local osteogenic and non-osteogenic responses.

Keywords: Disuse; Finite element analysis; Mechanical loading; Mechanical strain; Osteocyte; Sclerostin
Links

DOI: 10.1007/s00198-011-1656-4

PubMed: 21573880

WoS: 000301790500004
History

Received: 2010-12-23

Accepted: 2011-04-20

Online: 2011-05-15

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