MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect

Abstract

Aseptic prosthetic loosening (APL) often leads to the failure of prostheses. It is inseparable from wear-particle-induced macrophage-mediated inflammatory responses and osteolysis. Mg2+ is a metal ion with excellent anti-inflammatory properties. Herein, Mg2+ was introduced into a nanomedicine (MgO nanoparticles (MNPs)) to protect against APL. MNPs could be phagocytized by macrophages and gradually degraded intracellularly. Following MNPs treatment, lipopolysaccharide (LPS)-activated macrophages polarized into deeper M1 phenotype at 6 h but then switched to the M2 phenotype at 48 h. Furthermore, the MNPs suppressed the titanium (Ti) particle-induced osteoclastogenesis and osteolysis in vivo. However, the MNPs exhibited no impact on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and even inhibited osteogenesis in vitro. The contrary results between the in vitro and in vivo experiments imply that macrophages are the key factor in the inhibited osteoclastogenesis in vivo because the pathogenic process of APL is mainly attributed to macrophages, osteoblasts, and osteoclasts. Accordingly, an indirect coculture system was designed that considers the immunomodulatory effect of macrophages. RANKL-induced osteoclastogenesis was significantly inhibited under the influence of MNPs in the indirect coculture system. Taken together, the MNPs inhibited the inflammatory responses of macrophages provoked by the Ti particles and thus regulated the expressions of RANKL and OPG in osteoblasts to suppress osteoclastogenesis. The target cell of MNPs was macrophages but not osteoclasts, indicating the importance of the immunomodulatory effect of macrophages. These results collectively demonstrated that MNPs can prevent APL and other osteolysis-related diseases.

Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis

“…This antagonizing action on RANKL prevents osteoclast differentiation, which, in turn, may prevent bone resorption. These results are in agreement with the findings reported in earlier studies. − TRAP is one of the important gene associated with osteoclast differentiation; therefore, the expression level of TRAP was studied in differentiated RAW 267.4 cells. The results revealed that both MSN and MSN-SH caused reduction in the expression levels of TRAP, as evident in the figure. − Thus, MSN-SH promotes osteogenesis by upregulating the osteogenic genes, such as ALP, RUNX-2, OCN, and OPN and, at the same time, by inhibiting osteoclastogenesis by downregulating osteoclastic gene expression, such as RANKL and TRAP.…”

Photoluminescent carbon dots (PCDs) from sour apple: a biocompatible nanomaterial for preventing UHMWPE wear-particle induced osteolysis via modulating Chemerin/ChemR23 and SIRT1 signaling pathway and its bioimaging application

“…Implant-based particle debris, including UHMWPE, elicits a systemic immunological response and attracts monocytic cells to phagocytoze granules, resulting in the induction of ROS stress and augmented the secretion of pro-inflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-8, all of which make a significant participation to osteolysis [ 80 ]. Oxidative stress caused by ROS is one of the factors that cause osteoclasts to accelerate bone resorption [ 20 ].…”

Sequential activation of M1 and M2 phenotypes in macrophages by Mg degradation from Ti-Mg alloy for enhanced osteogenesis

“…As cells of innate immunity, macrophages are among the first batch of cells recruited to biomaterial surface after the implantation surgery. The high plasticity of macrophages allows them to switch their functions from one to another under various kinds of stimuli such as biomaterial surface characteristics, bioactive inorganic ions and immuno-modulatory biomolecules [11][12][13]. According to the surface markers and functions, macrophages could be roughly classified as pro-inflammatory M1 and anti-inflammatory M2 phenotypes [14].…”