The balance between endotoxin accumulation and clearance during particle‐induced osteolysis in murine calvaria

Abstract

Bacterial endotoxin may contribute to aseptic loosening of orthopedic implants even in the absence of clinical or microbiological evidence of infection. One potential source of endotoxin during aseptic loosening is systemically circulating endotoxin, derived from intestinal flora, minor infections, or dental procedures, that may bind to wear particles. The current study demonstrates that systemically derived endotoxin accumulates when 'endotoxin-free' titanium and polyethylene particles are implanted on murine calvaria. Time-course experiments and experiments using germfree mice rule out the possibility that the observed endotoxin accumulation may be due to bacterial contamination. In contrast, endotoxin is cleared from titanium particles that originally carry high amounts of adherent endotoxin. The mechanism of endotoxin clearance is not dependent on induction of a respiratory burst. Taken together, these results indicate that a balance between endotoxin accumulation and endotoxin clearance controls the steady-state level of endotoxin surrounding orthopedic wear particles implanted on murine calvaria. This balance may regulate the rate of osteolysis in the murine calvaria model as well as in patients with aseptic loosening. ß

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…This translocation of PAMPs from the gut can be increased by minor surgical procedures, such as colonoscopy, a high-fat diet, or even a single high-fat meal [3,14,52,71,84]. Also consistent with the possibility that circulating PAMPs could traffic to the periprosthetic tissue and induce inflammation locally are the findings that total joint arthroplasty increases circulating LPS levels [113] and that LPS from the circulation accumulates around ''endotoxin-free'' particles after implantation in rodents [104,114]. The local effects of the PAMPs can also include increased corrosion of titanium surfaces, which in turn can increase PAMP binding to the surface [6].…”

Effects of AS-cast and wrought cobalt-chrome-molybdenum and titanium-aluminium-vanadium alloys on cytokine gene expression and protein secretion in J774A.1 macrophages

“…These findings can be explained by the fact that macrophages express and secrete cytokines independently of the internalization process (Bi et al, 2002;Fritz et al, 2006;Nakashima et al, 1999). In physiological environment adherent endotoxin is unavoidable (Tatro et al, 2006) and may also contribute to the pro-inflammatory response generated by the foreign objects in the body. Endotoxin is ubiquitous remnants from gram-negative cell walls, with a strong pro-inflammatory capacity.…”

“…Three mm thick discs were machined out of 15 mm cylinders of the materials. To achieve a physiological endotoxin level (Tatro et al, 2006) discs were cleansed in a single cycle as previously described (Ragab et al, 1999). Endotoxin testing was done by Cambrex testing services (Cambrex Europe, Verviers, Belgium), and to extract endotoxin from the surface of the discs they were first placed on a shaking plate for 10 minutes followed by 30 minutes in an ultrasonic bath.…”

Presence of interleukin-17C in the tissue around aseptic loosened implants

“…The main long-term complication of an initially stable prosthesis is aseptic loosening [1][2][3]. Inflammation induced by wear particles of the prosthesis is considered to be the major cause of aseptic loosening [4,5] with some bacterial components from wounds and intestines are suspected to contribute to the particle-induced inflammation [6][7][8][9]. This inflammation is characterised by macrophage infiltration and proinflammatory cytokine secretion, and the pattern of cytokines consists of tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6) [10][11][12].…”

“…This inflammation is characterised by macrophage infiltration and proinflammatory cytokine secretion, and the pattern of cytokines consists of tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6) [10][11][12]. After phagocytosis or the contact of the implant wear debris with the adhering bacterial components [6][7][8][9][13][14][15][16][17], the nuclear transcription factor-kappa B (NFkappa B) of the macrophage is activated, and the macrophages express the above mentioned proinflammatory cytokines in response [11,12,18]. These proinflammatory cytokines disrupt the local balance of osteogenesis and osteolysis through the proliferation of osteoclasts and the inhibition of osteoblasts [12,[19][20][21].…”