High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis.

Autor: de Munter W; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Wouter.deMunter@radboudumc.nl., van den Bosch MH; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Martijn.vandenBosch@radboudumc.nl., Slöetjes AW; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Annet.Sloetjes@radboudumc.nl., Croce KJ; Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: KCroce@partners.org., Vogl T; Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: Vogl@uni-muenster.de., Roth J; Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: RothJ@uni-muenster.de., Koenders MI; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Marije.Koenders@radboudumc.nl., van de Loo FA; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Fons.vandeLoo@radboudumc.nl., van den Berg WB; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Wim.vandenBerg@radboudumc.nl., van der Kraan PM; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Peter.vanderKraan@radboudumc.nl., van Lent PL; Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Peter.vanLent@radboudumc.nl.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2016 May; Vol. 24 (5), pp. 844-55. Date of Electronic Publication: 2015 Dec 12.
DOI: 10.1016/j.joca.2015.11.016
Abstrakt: Objective: A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels independent of weight.
Method: Wild type (WT), Apoe(-)(/-), S100a9(-/-) and Apoe(-)(/-)S100a9(-/-) mice (C57BL/6 background) received a standard or cholesterol-rich diet. Experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 10 and day 36.
Results: Although minimal differences in cartilage damage were found between the WT and ApoE(-)(/-) mice, increased synovial thickening was found in the latter. Thirty-six days after OA-induction, ApoE(-)(/-) mice on a standard diet showed increased ectopic bone formation, particularly at the medial collateral ligament, compared with OA in WT mice. Furthermore, a significant increase in synovial gene expression of both S100a8 and S100a9 and S100A8/S100A9 protein levels was found in ApoE(-)(/-) mice, suggesting an activated inflammatory status of synovial cells. In both ApoE(-)(/-) and WT mice, addition of a cholesterol-rich diet resulted in excessive bone formation in the medial collateral ligament at late-time-point OA. Interestingly, at the early time point, proteoglycan deposition was already significantly increased in ApoE(-)(/-) mice compared with WT mice. Mice deficient for both ApoE and S100a9 also showed increased ectopic bone formation, but not synovial activation, suggesting a role for S100-proteins in cholesterol-mediated synovial activation.
Conclusions: Increased cholesterol levels strongly elevate synovial activation and ectopic bone formation in early-stage collagenase-induced OA.
(Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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