Cell-Tethered Ligands Modulate Bone Remodeling by Osteoblasts and Osteoclasts



The goals of the present study are to establish an in vitro co-culture model of osteoblast and osteoclast function and to quantify the resulting bone remodeling. The bone is tissue engineered using well-defined silk protein biomaterials in 2D and 3D formats in combination with human cells. Parathyroid hormone (PTH) and glucose-dependent insulinotropic peptide (GIP) are selected because of their roles in bone remodeling for expression in tethered format on human mesenchymal stem cells (hMSCs). The cell-modified biomaterial surfaces are reconstructed from scanning electron microscopy images into 3D models for quantitative measurement of surface characteristics. Increased calcium deposition and surface roughness are found in 3D surface models of silk protein films remodeled by co-cultures containing tethered PTH, and decreased surface roughness is found for the films remodeled by tethered GIP co-cultures. Increased surface roughness is not found in monocultures of hMSCs expressing tethered PTH, suggesting that osteoclast-osteoblast interactions in the presence of PTH signaling are responsible for the increased mineralization. These data point towards the design of in vitro bone models in which osteoblast-osteoclast interactions are mimicked for a better understanding of bone remodeling.