Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Abstract

BackgroundPeriprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.MethodsWe used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.ResultsBone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.ConclusionsAs anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

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“…However we found no effect of LIR on calcitonin secretion while studies have reported that both Ex-4 and LIR stimulate calcitonin secretion (63,64). Our data are not completely consistent with this mechanism since we observed an increase in resorption surfaces with GLP-1 agonists whereas other studies have reported that calcitonin decreased resorption surfaces (65).…”

The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis

“…However, the observed reduction in PIO in a-CGRP-deficient mice could have been attributed to a compensatory effect of CT. Huebner et al [16] reported the dual action of CT, as an inhibitor of both bone formation and bone resorption, which could be highly relevant in conditions associated with increased bone resorption, such as PIO. Therefore, further investigations on Calca À/À mice with a combined deficiency in a-CGRP and CT were performed and showed pronounced osteolysis in UHMWPE particle-treated mice at the age of 3 months, while additional substitution of CT in these animals revealed a reduction in PIO [11]. Thus, activation of the CTR could play a crucial role in the PIO process.…”

“…In the presence of UHMWPE particles, a reduced http://dx.doi.org/10.1016/j.actbio.2014. 11.051 1742-7061/Ó 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.…”

“…In an attempt to assess the impact of CT/a-CGRP in the presence of UHMWPE particles, mice with an isolated or combined deficiency of a-CGRP and CT were studied [11][12][13]. While UHMWPE particles revealed pronounced osteolysis in wild-type mice, different observations in a-CGRP-and CT-deficient mice were made [14].…”

Are Biologic Treatments a Potential Approach to Wear- and Corrosion-related Problems?

“…Addition of other agents, including berberine, captropril, dynastat, and N-acetyl-L-cysteine, decreased particle-dependent inflammation and associated osteolysis [14,16,60,61]. In studies taking advantage of knockout mutations, protein replacement of calcitonin and IL-6 increased bone and decreased inflammation, respectively, in calcitonin-negative and IL-6-negative animals [11,19]. The mouse model of osteolysis also allowed agents to be tested locally at the site of the applied particles.…”