Curcumin Attenuates Titanium Particle-Induced Inflammation by Regulating Macrophage Polarization In Vitro and In Vivo

Abstract

Periprosthetic inflammatory osteolysis and subsequent aseptic loosening are commonly observed in total joint arthroplasty. Other than revision surgery, few approved treatments are available for this complication. Wear particle-induced inflammation and macrophage polarization state play critical roles in periprosthetic osteolysis. We investigated the effects of curcumin, a polyphenol extracted from Curcuma longa, on titanium (Ti) particle-induced inflammation and macrophage polarization in vitro using the murine cell line RAW 264.7 and in vivo using a murine air pouch model. The expression of specific macrophage markers was qualitatively analyzed by immunofluorescence (inducible nitric oxide synthase and CD206) and quantitatively analyzed by flow cytometry (CCR7 and CD206), representing M1 and M2 macrophages, respectively. Our results show that curcumin induced a higher percentage of M2 macrophages together with a higher concentration of anti-inflammatory cytokine IL-10, and a lower percentage of M1 macrophages with a lower concentration of pro-inflammatory cytokines (TNF-α and IL-6). The genes encoding CD86 (M1) and CD163 (M2), two additional markers, were shifted by curcumin toward an M2 phenotype. C57BL/J6 mice were injected with air and Ti particles to establish an air pouch model. Curcumin reduced cell infiltration in the pouch membrane and decreased membrane thickness. The analysis of exudates obtained from pouches demonstrated that the effects of curcumin on macrophage polarization and cytokine production were similar to those observed in vitro. These results prove that curcumin suppresses Ti particle-induced inflammation by regulating macrophage polarization. Thus, curcumin could be developed as a new therapeutic candidate for the prevention and treatment of inflammatory osteolysis and aseptic loosening.

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

“…Furthermore, curcumin is known as "the king of spices" on account of its epigenetic regulatory properties with regard to preventing cancer and neurologic and inflammatory diseases, such as breast carcinoma, osteogenic sarcoma, osteoarthritis, and neurocognitive disorders [11][12][13][14]. A recent study by Li et al [15] showed that curcumin could suppress inflammation caused by titanium particles by regulating the polarization of macrophages. Therefore, curcumin could be developed as a treatment for inflammatory osteolysis and aseptic loosening.…”

Effect of silkworm peptide on inducting M1 type polarization and Th1 activation via TLR2‐induced MyD88‐dependent pathway

“…M1 macrophages mainly secrete NO, IL‐6, IL‐12 and TNF‐α, and other inflammatory factors (Wang et al., ). M2 macrophages secrete a higher concentration of the anti‐inflammatory factor IL‐10 (Li et al., ). Therefore, this study used ELISA to detect the NO, IL‐6, IL‐12, IL‐10, and IL‐1β levels in the culture supernatant of mouse peritoneal macrophages after treated with different doses of silkworm peptides in Lewis lung cancer model mice, and it was used to confirm the effect of silkworm peptide on the polarization type of mouse macrophages.…”

“…M2 macrophages secrete a higher concentration of the anti-inflammatory factor IL-10 (Li et al, 2017). Therefore, this study used ELISA to detect the NO, IL-6, IL-12, IL-10, and IL-1β levels in the culture su- Th1 activation of CD4 + T cells can be through two completely different pathways: One pathway is to induce Th1 activation through indirect action; that is, the antigen first activates antigen-presenting cells in vivo, and then the activated antigen-presenting cells extract the processed antigen to CD4 + T cells and induce Th1 activation; the other pathway is to induce Th1 activation by direct action; that is, the antigen does not need to interact with antigen-presenting cells to directly induce Th1 activation in CD4 + T cells.…”

Curcumin has immunomodulatory effects on RANKL‐stimulated osteoclastogenesis in vitro and titanium nanoparticle‐induced bone loss in vivo

“…8 Wear debris-stimulated M0 macrophages turn into proinflammatory macrophages (M1 phenotype) and subsequently produce of proinflammatory chemokines. 12 Therefore, we have been suggested that the modulation of M1/M2 macrophages represents a potential therapeutic strategy to alleviate wear debris-mediated osteolysis. However, M2 phenotype macrophages secrete anti-inflammatory cytokines and create an anti-inflammatory microenvironment, which subsequently inhibit the differentiation and formation of osteoclasts.…”