Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet.

Autor: Kozijn AE; Metabolic Health Research, TNO, Leiden, the Netherlands; Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands., Tartjiono MT; Metabolic Health Research, TNO, Leiden, the Netherlands., Ravipati S; Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom., van der Ham F; Metabolic Health Research, TNO, Leiden, the Netherlands., Barrett DA; Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom., Mastbergen SC; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands., Korthagen NM; Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Lafeber FPJG; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands., Zuurmond AM; Metabolic Health Research, TNO, Leiden, the Netherlands., Bobeldijk I; Metabolic Health Research, TNO, Leiden, the Netherlands., Weinans H; Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands., Stoop R; Metabolic Health Research, TNO, Leiden, the Netherlands. Electronic address: Reinout.Stoop@tno.nl.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2019 Jan; Vol. 27 (1), pp. 118-128. Date of Electronic Publication: 2018 Sep 22.
DOI: 10.1016/j.joca.2018.09.007
Abstrakt: Objective: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of 'metabolic' OA.
Design: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets.
Results: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups.
Conclusions: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.
(Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: