Curcumin Inhibits Polyethylene-Induced Osteolysis via Repressing NF-κB Signaling Pathway Activation

Abstract

Background/Aims: Aseptic loosening is a common reason for failed artificial hip replacement after total hip arthroplasty. Aseptic loosening is mostly the result of wear debris that causes osteolysis and weakens the structures that support the prosthesis. Wear debris plays a crucial role in osteolysis during the loosening process, and polyethylene (PE) particles are found as wear debris more frequently than any other type of particle. In the absence of effective therapeutic agents, osteolysis has been hard to treat. Previous studies have demonstrated that curcumin influences signalosome-associated kinases and the proteasome-ubiquitin system during osteoclastogenesis. The aims of this study were to explore the anti-osteolysis effect of curcumin and if possible to identify the signaling pathway involved in a model of PE-induced osteolysis. Methods: Differentiation of osteoclasts was induced in vitro by PE particles in RAW264.7 (monocyte/macrophage) cells and in vivo by calvarial and air pouch models of osteolysis established by PE stimulation in mice. We performed a set of TRAP staining, realtime polymerase chain reaction (PCR), and Western blot experiments to evaluate the anti-osteolytic effect of curcumin by comparing specimens that were exposed and not exposed to curcumin. Results: Curcumin had a promising inhibitory effect on osteolysis induced by wear debris and suppressed the RANK/c-Fos/NFATc1 signaling pathway. Conclusion: Curcumin can prevent PE-induced osteolysis and bone loss. An inhibitory effect on the RANK/c-Fos/NFATc1 signaling pathway may explain the anti-osteolysis activity of curcumin.

Targeted Delivery of Curcumin to Polyethylene-Induced Osteolysis by Magnetically Guided Zoledronate-Anchored Poly Lactic-Co-Glycolic Acid Nanoparticles via Repressing NF-κB Signaling

“…After RANKL treatment, OC differentiation of RAW 264.7 cells produced large, round, and red-stained multinucleated OCs in the PBS group ( Figure 3D). In contrast, after curcumin treatment, the number of mature TRAP-positive OCs decreased (Figure 2E, p < 0.05), signifying that curcumin could attenuate OC formation, which was consistent with our previously study (An et al, 2018). Similarly, the number of TRAP-positive OCs significantly decreased after ZSCNP treatment ( Figure 3E, p < 0.05), indicating that curcumin in ZSCNPs could effectively reduce OC formation, which was in line with the in vitro curcumin release experiment in this study.…”

“…Studies have shown that inhibiting the activity of IKK can lead to repressing the phosphorylation of the p65 subunit of NF-kB, thereby inhibiting the nuclear ectopic of NF-kB to suppress downstream pathways (Fiume et al, 2015;Pontoriero et al, 2019). Furthermore, our group verified that curcumin can inhibit the entire NF-κB activation process by inhibiting the effect of IKK, preventing polyethylene (PE)-induced osteolysis and bone loss, and repressing the RANK/c-Fos/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway (An et al, 2018). However, to the best of our knowledge, no studies have reported on the benefits of curcumin-loaded NPs in inhibiting PE-induced osteolysis.…”

“…On the seventh day, cells were fixed in 4% paraformaldehyde, washed with PBS, and then subjected to tartrate-resistant acid phosphatase (TRAP) staining using a leukocyte acid phosphatase cytochemistry kit (Sigma-Aldrich). TRAP-positive cells were defined as containing three or more nuclei and counted as mature OCs using a light microscope, and the TRAP activity assay was performed as previously described (An et al, 2018;Park et al, 2018;Ouyang et al, 2019).…”

“…After 14 days, blood samples were collected for serum biochemistry assays. The calvarial bones were collected for micro CT imaging (Viva CT-80, SCANCO Medical AG, Zurich, Switzerland), and relevant bone volume fractions (bone volume/tissue volume, BV/TV, %) were obtained to analyze the effects of ZSCNPs on calvarial osteolysis mice and were calculated as described previously (Panmekiate et al, 2015;Huynh et al, 2017;An et al, 2018;Ouyang et al, 2019). Then, the samples were subjected to TRAP staining to assess OC formation.…”

“…Curcumin is a small molecular weight polyphenol that is extracted from turmeric rhizomes of the ginger family. Recent studies have shown that curcumin has a wide range of biological and pharmacological activities, such as anti-inflammatory, anticoagulation, anti-arteriosclerosis, anti-oxidant, anti-tumor and particle-induced osteolysis activity (Anand et al, 2007;Gautam et al, 2007;Wilken et al, 2011;Chin, 2016;Kunwar and Priyadarsini, 2016;Li et al, 2017;An et al, 2018). However, curcumin has a short circulation half-life, poor hydrophilicity, and low bioavailability, which extremely limit its pharmacological activity and biomedical applications (Wilken et al, 2011).…”