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Disease Markers
Volume 2015, Article ID 196589, 9 pages
http://dx.doi.org/10.1155/2015/196589
Research Article

Monocyte Proteomics Reveals Involvement of Phosphorylated HSP27 in the Pathogenesis of Osteoporosis

1National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai 400012, India
2Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
3Mazumdar Shaw Centre for Translational Research, Narayana Health, Bangalore 560099, India

Received 7 February 2015; Revised 30 March 2015; Accepted 7 April 2015

Academic Editor: Lance A. Liotta

Copyright © 2015 Bhavna Daswani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peripheral monocytes, precursors of osteoclasts, have emerged as important candidates for identifying proteins relevant to osteoporosis, a condition characterized by low Bone Mineral Density (BMD) and increased susceptibility for fractures. We employed 4-plex iTRAQ (isobaric tags for relative and absolute quantification) coupled with LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) to identify differentially expressed monocyte proteins from premenopausal and postmenopausal women with low versus high BMD. Of 1801 proteins identified, 45 were differentially abundant in low versus high BMD, with heat shock protein 27 (HSP27) distinctly upregulated in low BMD condition in both premenopausal and postmenopausal categories. Validation in individual samples () using intracellular ELISA confirmed that total HSP27 (tHSP27) as well as phosphorylated HSP27 (pHSP27) was elevated in low BMD condition in both categories (). Further, using transwell assays, pHSP27, when placed in the upper chamber, could increase monocyte migration () and this was additive in combination with RANKL (receptor activator of ligand) placed in the lower chamber (). Effect of pHSP27 in monocyte migration towards bone milieu can result in increased osteoclast formation and thus contribute to pathogenesis of osteoporosis. Overall, this study reveals for the first time a novel link between monocyte HSP27 and BMD.