Abstract

The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening. Our study included 37 patients who underwent revision surgery due to hip osteolysis and aseptic loosening and 31 patients who underwent primary total hip arthroplasty. Using antibody arrays, we evaluated the serum levels of 320 proteins in four patients from each group. The results showed differences in insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations, which we then quantified using enzyme-linked immunosorbent assay tests in all study patients. The results confirmed that serum IGFBP-1 concentrations were higher in the revision surgery patients than in the hip arthroplasty patients. In vitro studies showed that exposure of human osteoblasts to titanium particles induced an IGFBP-1 release that further increased when exposure to particles was performed in media conditioned by human M1 macrophages. These findings suggest that elevated serum IGFBP-1 levels in patients with aseptic loosening can arise from increased local IGFBP-1 production in the inflammatory environment of the periprosthetic bed.

Highlights

  • The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes

  • We found that serum insulin-like growth factor binding protein-1 (IGFBP-1) levels are higher in patients with hip aseptic loosening than in patients who underwent primary total hip arthroplasty, and we evaluated whether this protein could serve as a biomarker for this disabling joint condition

  • To determine whether the source of elevated circulating insulin-like growth factor-binding protein 1 (IGFBP-1) levels is the periprosthetic cellular environment, we investigated the secretion of the protein in cultures of human osteoblasts and macrophages treated with titanium particles, as a model of metallic wear debris, or with media conditioned by osteoblasts or macrophages exposed to these particles

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Summary

Introduction

The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Changes in the levels of some of these factors have been detected in synovial fluid and serum from patients experiencing aseptic loosening and have been proposed as markers of this condition These factors include certain pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6 and IL-8; bone metabolism-specific molecules such as receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin and anti-inflammatory mediators such as IL-1013–15, among others. We found that serum insulin-like growth factor binding protein-1 (IGFBP-1) levels are higher in patients with hip aseptic loosening than in patients who underwent primary total hip arthroplasty, and we evaluated whether this protein could serve as a biomarker for this disabling joint condition. To determine whether the source of elevated circulating IGFBP-1 levels is the periprosthetic cellular environment, we investigated the secretion of the protein in cultures of human osteoblasts and macrophages treated with titanium particles, as a model of metallic wear debris, or with media conditioned by osteoblasts or macrophages exposed to these particles

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