Caffeic Acid Phenethyl Ester Abrogates Bone Resorption in a Murine Calvarial Model of Polyethylene Particle-Induced Osteolysis

Abstract

Particle-induced bone loss by osteoclasts is a common cause of aseptic loosening around implants. This study investigates whether caffeic acid phenethyl ester (CAPE), a potent and specific inhibitor of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 and nuclear factor kappa B, at a low dose reduces bone resorption in a murine calvarial model of polyethylene (PE) particle-induced osteolysis. The effects of particles and CAPE treatment on gastrointestinal tract (GIT) histopathology were also evaluated. Mice were scanned using in vivo animal micro-computed tomography (μCT) as a baseline measurement. PE particles (2.82 × 10(9) particles/mL) were implanted over the calvariae on day 0. CAPE was administered subcutaneously (1 mg/kg/day) at days 0, 4, 7 and 10. Mice were killed at day 14 and serum was analysed for Type-1 carboxyterminal collagen crosslinks (CTX)-1 and osteoclast-associated receptor (OSCAR) levels. Ex vivo μCT scans were conducted to assess bone volume (BV) change and percentage area of calvarial surface resorbed. Calvarial and GIT tissue was processed for histopathology. By day 14, PE particles significantly induced calvarial bone loss compared with control animals as evidenced by resorption areas adjacent to the implanted PE in three-dimensional μCT images, an increase in percentage of resorbed area (p = 0.0022), reduction in BV (p = 0.0012) and increased Tartrate-resistant acid phosphatase positive cells. Serum CTX-1 (p = 0.0495) and OSCAR levels (p = 0.0006) significantly increased in the PE implant group. CAPE significantly inhibited PE particle-induced calvarial osteolysis, as evidenced by a significant reduction in surface bone resorption (p = 0.0012) and volumetric change (p = 0.0154) compared with PE only, but had no effect on systemic CTX-1. Neither particles nor CAPE had an effect on GIT histopathology.

Parthenolide reduces empty lacunae and osteoclastic bone surface resorption induced by polyethylene particles in a murine calvarial model of peri‐implant osteolysis

“…At day 14 postsurgery, BV in the PE group was significantly reduced when compared with the control group, consistent with the development of osteolysis at that time point as previously reported. 14,24 PAR significantly inhibits NF-jB and osteoclastogenesis in vitro 30 as well as LPS- 15 and PE-induced 12 osteolysis in mice. In the current study, PAR administration (1 mg/kg/3 days) to PE-implanted mice did not significantly affect the BV after 14 days when compared with the baseline BV.…”

“…, suggesting that the particles may also induce resorption at a distance. 24 This is most likely due to mediators induced by PE particles stimulating osteoclast activity in the bone marrow. This may also occur within the bone and on the trabeculae.…”

“…This murine model of PE particle-induced osteolysis was based on a model developed by Wedemeyer et al 14,24 Twenty-four 6-to 8-week LPS-resistant 25 C3H/HEJ mice were randomly allocated to four groups of six: control (no disease and no treatment); PAR only (no disease but treated with PAR); PE only (disease and no treatment); and PE 1 PAR (disease with PAR treatment). Ethical approval was obtained from the Animal Ethics Committees of the University of Adelaide (M-2001-070) and SA Pathology (106/10) and complied with the National Health and Medical Research Council (Australia) Code of Practice for Animal Care in Research and Teaching (2014).…”

“…For each segmented VOI (rectangular slab) visualized in 3D of the day 14 scans, two orthogonal screen shot images were taken (software ParaView). 24 One image visualized the outer skull surface and one the inner surface [ Fig. 1(e-l)].…”

Quantifying shape changes of silicone breast implants in a murine model using in vivo micro‐CT

“…The micro‐CT scanning window, 18 mm in length and 35 mm in width, was centered on the implants. The scanner settings were as follows: 8.65 µm isotropic pixel size, source voltage 60 kV, current 100 µA, rotation step 0.8°, rotation over 180°, no frames averaging, aluminum filter 1‐mm thick, total scanning time 20 min per mouse . The cross‐section images were reconstructed using a filtered back‐projection algorithm (NRecon software, SkyScan‐Bruker, Kontich, Belgium) and saved as 8‐bit gray level images.…”