Osteoclast Precursor Membrane-Coated Nanoparticles Loaded With Abaloparatide Enable Dual Modulation of Osteoclast and Osteoblast Differentiation.

Osteoporosis (OP) arises from an imbalance between bone-resorbing osteoclasts and bone-forming osteoblasts. This study investigated whether abaloparatide-loaded nanoparticles coated with osteoclast precursor cell membranes (ANPs) can modulate the differentiation of both cell types in vitro. ANPs were prepared by incubating abaloparatide with membranes isolated from RAW 264.7 cells. Nanoparticle characterization included size, charge, drug release, and cellular uptake. Osteoclast and osteoblast differentiation were assessed using western blotting, staining assays (ALP, ARS, TRAP), flow cytometry, and EdU proliferation assays. A Transwell co-culture system was used to model cell-cell interactions. ANPs were spherical (~ 105 nm), exhibited sustained drug release (58% at day 5), and were efficiently internalized by both cell types. In osteoclast precursors, ANPs suppressed RANKL-induced differentiation, downregulating CTSK, NFATc1, and TRAP without affecting cell viability. In osteoblasts, ANPs enhanced mineralization and upregulated Runx2, Osterix, and Osteocalcin. In co-culture, ANPs reduced CTX-I and increased P1NP secretion, indicating a shift toward bone formation. ANPs represent a promising dual-action platform for potential application in OP, capable of simultaneously suppressing osteoclast activity and enhancing osteoblast function through targeted and sustained drug delivery in vitro.