Abstract
Wear particle-induced chronic inflammation and osteoclastogenesis are two critical factors in the osteolytic process. Curcumin (CUR) is an active compound of the medicinal herb Curcuma longa and has anti-inflammatory and antiosteoclastogenic properties. Our study tested the hypothesis that CUR might attenuate polymethylmethacrylate- (PMMA-) induced inflammatory osteolysis using mouse calvaria osteolysis model in vivo and in vitro. The mice were divided into four groups: phosphate-buffered saline group, CUR, PMMA, and PMMA + CUR groups. Three days before PMMA particle implantation, the mice were intraperitoneally injected with CUR (25 mg/kg/day). Ten days after the operation, the mouse calvaria was harvested for microcomputed tomography, histomorphometry, and molecular biology analysis. As expected, CUR markedly reduced the secretion of tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 in the calvarial organ culture. Moreover, CUR suppressed osteoclastogenesis and decreased bone resorption in vivo compared with PMMA-stimulated calvaria. Furthermore, CUR downregulated the osteoclast-specific gene expression and reversed the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin messenger RNA and protein ratio in PMMA particle-stimulated mice. These results suggest that CUR attenuated PMMA particle-induced inflammatory osteolysis by suppressing the RANKL signaling pathway in the murine calvarium, which could be a candidate compound to prevent and treat AL.
Highlights
Hip arthroplasties are among the most successful procedures for end-stage joint diseases
The μCT image revealed that particle implantation elicits localized inflammatory and osteolytic responses that significantly widened the cranial suture width and bone porosity in the untreated mice (PMMA group) compared with the phosphate-buffered saline (PBS) group
According to the 3D image, the PMMA group revealed a significant decrease in all four parameters (BMD, bone volume/tissue volume (BV/TV), number of porosities, and percentage of total porosity) compared with the PBS group (p < 0 001; Figures 1(b), 1(c), 1(d), and 1(e))
Summary
Hip arthroplasties are among the most successful procedures for end-stage joint diseases. Periprosthetic osteolysis and subsequent aseptic loosening (AL) are the main causes of implant failure and affect approximately one-third of patients 10–20 years postoperatively [1,2,3,4]. Wear particles generated at joint articulations and nonarticulating interface play critical roles in periprosthetic osteolysis pathogenesis [2, 5, 6]. Revision surgery for wear particleinduced osteolysis is the only effective treatment for AL. It is associated with high morbidity, mortality, complication rates, and poor functional outcomes [1, 5]. The majority of research in relation to AL has focused on the mechanisms involved in the modulation of inflammation and differentiation of osteoclast precursors into mature osteoclasts at the molecular level through pharmacological intervention [6,7,8,9,10]
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