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

Abstract

Photoluminescent nanomaterials have been widely employed in several biological applications both in vitro and in vivo. For the first time, we report a novel application of sour apple-derived photoluminescent carbon dots (PCDs) for reducing ultra-high molecular weight polyethylene (UHMWPE) wear particle-induced osteolysis using mouse calvarial model. Generally, aseptic prosthetic loosening seems to be a significant postoperative problem for artificial joints replacement, which is mainly contributed by UHMWPE-induced osteolysis. Hence, inhibiting osteoclastic bone-resorption could minimize UHMWPE-induced osteolysis for implant loosening. Prior to osteolysis studies, the prepared sour apple-derived PCDs were employed for bioimaging application. As expected, the prepared PCDs effectively inhibited the UHMWPE particle-induced osteoclastogenesis in vitro. The PCDs treatment effectively inhibited the UHMWPE-induced osteoclast differentiation, F-actin ring pattern, and bone resorption in vitro. Also, the PCDs reduced the UHMWPE-induced ROS stress as well as the expression level of pro-inflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-8. Further, the qPCR and western blot results hypothesized that PCDs inhibited the UHMWPE wear particle-induced osteolysis through suppressing chemerin/ChemR23 signaling and NFATc1 pathway, along with upregulation of SIRT1 expression. Overall, these findings suggest that the synthesized PCDs could be a potential therapeutic material for minimizing UHMWPE particle-induced periprosthetic osteolysis to avoid postoperative complications.

Insight into the Molecule Impact of Critical-Sized UHMWPE-ALN Wear Particles on Cells by the Alginate-Encapsulated Cell Reactor

“…Figure 4 shows the levels of cytokines secreted from macrophages after being co-cultured with critical-sized UHMWPE-ALN wear particles in cell reactors for 1, 7, and 14 d. The secreted levels of TNF-α ( Figure 4 a) and IL-6 ( Figure 4 b) of macrophages increased with time in different groups. Particularly, the secreted levels of TNF-α and IL-6 cytokines of macrophages in the Alg + MPs + UHMWPE-ALN and Alg + MPs + UHMWPE groups were significantly higher than those in the Alg + MPs group, which demonstrated that the critical-sized wear particles would stimulate the secretion of cytokines from macrophages, which was analogous to the findings of Li et al [ 21 ]. However, the secreted levels of TNF-α and IL-6 cytokines from macrophages in the Alg + MPs + UHMWPE-ALN group were significantly lower than those in the Alg + MPs + UHMWPE group.…”

Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases

“…Photoluminescent carbon dots (PCDs) from sour apples cured a mouse calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) wear particles. PCDs reduced UHMWPE-induced ROS stress and pro-inflammatory cytokine production to inhibit osteoclastogenesis and bone resorption in vitro [ 188 ].…”

Macrophages in aseptic loosening: Characteristics, functions, and mechanisms

“…Under the same settings, NF-κB can be activated by RANKL or LPS to augment particles-induced bone loss via the enhancement of osteoclastogenesis ( 206 , 207 ). Upstream stimuli-triggered NF-κB signaling could act on transcription factors (c-fos and NFATc1) and regulate the expression of osteoclastogenesis-related genes, thus promoting OC differentiation and functions ( 206 , 208 , 209 ).…”