Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes
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(2020) 21:78
RESEARCH ARTICLE
BMC Molecular and Cell Biology
Open Access
Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes H. Allison1, G. Holdsworth2 and L. M. McNamara1*
Abstract Background: Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression. Results: Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. Conclusions: This study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce proosteoclastogenic cell signalling between osteocytes and osteoclasts. Keywords: Mechanobiology, Estrogen deficiency, Sclerostin antibody, Osteoclastogenesis, Oscillatory fluid flow
* Correspondence: [email protected] 1 Mechanobiology and Medical Devices Research Group (MMDRG), Centre for Biomechanics Research (BioMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the
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