A Highly Bioactive Organic–Inorganic Nanoparticle for Activating Wnt10b Mediated Osteogenesis by Specifically Anchor CCN3 Protein

Organic–Inorganic hybrid PCS nanoparticles can bind to the TSP-1 and vWC structural domains on CCN3 protein through the synergistic action of silica hydroxyl and ester groups, resulting in conformational changes and functional activation. The activated CCN3 binds to Wnt10b, which activates the Wnt10b/β-catenin signaling pathway, ultimately promoting bone regeneration.

Abstract

The rapid and efficient bone regeneration is still in unsatisfactory outcomes, demonstrating alternative strategy and molecular mechanism is necessary. Nanoscale biomaterials have shown some promising results in enhancing bone regeneration, however, the detailed interaction mechanism between nanomaterial and cells/tissue formation is not clear. Herein, a molecular-based inorganic–organic nanomaterial poly(citrate-siloxane) (PCS) is reported which can rapidly enhance osteogenic differentiation and bone formation through a special interaction with the cellular surface communication network factor 3 (CCN3), further activating the Wnt10b/β-catenin signaling pathway. Further studies revealed that the CCN3 is a key bridge protein for transmitting the osteoinductive effects of nano PCS into the intracellular compartment and activating Wnt10b. Specifically, the molecular mechanism studies confirmed that the inorganic silicon hydroxyl and the organic ester group can bound to the Thrombospondin-1 (TSP-1) and von Willebrand factor type C repeat module (vWC) structural domains of CCN3 respectively. The special material-protein interaction induced a conformational change of CCN3 and activated the function of the TSP-1 structural domain, which is further associated with the binding and activation of Wnt10b signaling. This study reveals the first targets of nanobiomaterials to promote tissue regeneration through cellular interactions and provides new ideas for the development of materiobiology.