@article{7635ad9e9414414fb84ff02d56dc83c1,
title = "Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds",
abstract = "The instructive capabilities of extracellular matrix–inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration.",
author = "Xiaoyan Ren and Qi Zhou and David Foulad and Tiffany, {Aleczandria S.} and Dewey, {Marley J.} and David Bischoff and Miller, {Timothy A.} and Reid, {Russell R.} and He, {Tong Chuan} and Yamaguchi, {Dean T.} and Harley, {Brendan A.C.} and Lee, {Justine C.}",
note = "Funding Information: This work was supported by the U.S. Department of Veterans Affairs under award no. IK2 BX002442 (to J.C.L.), the Aramont Foundation (to T.A.M.), the Jean Perkins Foundation (to J.C.L.), and the Plastic Surgery Foundation under award no. 234813 (to J.C.L.). This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs Broad Agency Announcement for Extramural Medical Research through the award no. W81XWH-16-1-0566 (to B.A.C.H.). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Research reported in this publication was also supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award no. R21 DE026582 (to B.A.C.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We are grateful for the funding for this study provided by the NSF Graduate Research Fellowship DGE-1144245 (to M.J.D.). Publisher Copyright: {\textcopyright} 2019 The Authors, some rights reserved.",
year = "2019",
month = jun,
day = "12",
doi = "10.1126/sciadv.aaw4991",
language = "English (US)",
volume = "5",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "6",
}