Hydroxyapatite (HA) coated iron oxide (Fe(3)O(4)) magnetic nanoparticles have been shown to enhance osteoblast (bone forming cells) proliferation and osteoblast differentiation into calcium depositing cells (through increased secretion of alkaline phosphatase, collagen and calcium deposition) compared to control samples without nanoparticles. Such nanoparticles are, thus, very promising for numerous orthopedic applications including magnetically directed osteoporosis treatment. The objective of the current study was to elucidate the mechanisms of the aforementioned improved osteoblast responses in the presence of HA coated Fe(3)O(4) nanoparticles. Results demonstrated large amounts of fibronectin (a protein known to increase osteoblast functions) adsorption on HA coated Fe(3)O(4) nanoparticles. Specifically, fibronectin adsorption almost doubled when HA coated Fe(3)O(4) nanoparticle concentrations increased from 12.5 to 100 μg ml(-1), and from 12.5 to 200 μg ml(-1), a four fold increase was observed. Results also showed greater osteoblast gene regulation (specifically, osteocalcin, type I collagen and cbfa-1) in the presence of HA coated Fe(3)O(4) nanoparticles. Collectively, these results provide a mechanism for the observed enhanced osteoblast functions in the presence of HA coated iron oxide nanoparticles, allowing their further investigation for a number of orthopedic applications.