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.
Highlights
Total joint arthroplasty is a highly successful surgical technique used to relieve pain and improve both movement and the quality of life for patients with severe joint diseases [1]
The current study described the potential of curcumin to attenuate Ti particle-induced inflammation in vitro using a murine macrophage cell line, RAW 264.7, and in vivo using a murine air pouch model by regulating macrophage polarization to an M2 phenotype
The results were consistent with previous observations that curcumin induced a higher percentage of M2 macrophages and the trend was more significant after 4 days of culture
Summary
Total joint arthroplasty is a highly successful surgical technique used to relieve pain and improve both movement and the quality of life for patients with severe joint diseases [1]. The local inflammation induced by wear particles, which are generated at the interface of the implant and the bone, is critically important for understanding the underlying cause of osteolysis and consequent aseptic loosening [2]. After stimulated by wear particles, macrophages increase the expression of pro-inflammatory factors, including cytokines, chemokines, and other substances [3, 4]. One current hypothesis on macrophage polarization and plasticity has aroused interest in the pathogenesis of wear particle recognition and inflammatory osteolysis [5, 6]. M1 macrophages exhibit increased phagocytic activity and increased production of pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) to promote inflammation. Modulation of the macrophage activation state would appear to be a novel strategy for attenuating wear particle-induced inflammation [10]. Evidence is emerging that the modulation of macrophages from an M1 phenotype to an M2 phenotype is a viable method to reduce particle-induced inflammation [11,12,13]
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