1. Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds.
- Author
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Ren, Xiaoyan, Zhou, Qi, Foulad, David, Tiffany, Aleczandria S, Dewey, Marley J, Bischoff, David, Miller, Timothy A, Reid, Russell R, He, Tong-Chuan, Yamaguchi, Dean T, Harley, Brendan AC, and Lee, Justine C
- Subjects
Bone Regeneration ,Bone Resorption ,Bone and Bones ,Calcification ,Physiologic ,Cell Differentiation ,Chondroitin Sulfates ,Coculture Techniques ,Collagen Type I ,Cross-Linking Reagents ,Gene Expression ,Glycosaminoglycans ,Humans ,Mesenchymal Stem Cells ,Osteoclasts ,Osteogenesis ,Osteoprotegerin ,Primary Cell Culture ,Tissue Engineering ,Tissue Scaffolds ,Transgenes ,Calcification ,Physiologic - 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.
- Published
- 2019