High LDL levels lessen bone destruction during antigen-induced arthritis by inhibiting osteoclast formation and function.

Autor: Ascone G; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Giuliana.Ascone@radboudumc.nl., Di Ceglie I; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Irene.DiCeglie@radboudumc.nl., Walgreen B; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Birgitte.Walgreen@radboudumc.nl., Sloetjes AW; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Annet.Sloetjes@radboudumc.nl., Lindhout E; Future Diagnostics Solutions (FDx), Wijchen, the Netherlands. Electronic address: Lindhout.E@future-diagnostics.nl., Bot I; Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden, the Netherlands. Electronic address: I.Bot@lacdr.leidenuniv.nl., van de Loo FAJ; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Fons.vandeLoo@radboudumc.nl., Koenders MI; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Marije.Koenders@radboudumc.nl., van der Kraan PM; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Peter.vanderKraan@radboudumc.nl., Blom AB; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Arjen.Blom@radboudumc.nl., van den Bosch MHJ; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Martijn.vandenBosch@radboudumc.nl., van Lent PLEM; Department of Experimental Rheumatology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. Electronic address: Peter.vanLent@radboudumc.nl.
Jazyk: angličtina
Zdroj: Bone [Bone] 2020 Jan; Vol. 130, pp. 115140. Date of Electronic Publication: 2019 Nov 09.
DOI: 10.1016/j.bone.2019.115140
Abstrakt: Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by severe joint inflammation and bone destruction as the result of increased numbers and activity of osteoclasts. RA is often associated with metabolic syndrome, whereby elevated levels of LDL are oxidized into oxLDL, which might affect osteoclastogenesis. In this study, we induced antigen-induced arthritis (AIA) in Apoe -/- mice, which spontaneously develop high LDL levels, to investigate the effects of high LDL/oxLDL levels on osteoclast differentiation and bone destruction. Whereas basal levels of bone resorption were comparable between naive WT and Apoe -/- mice, induction of AIA resulted in a significant reduction of bone destruction in Apoe -/- mice as compared to WT controls. In line with that, the TRAP + area on the cortical bone was significantly decreased. The absence of Apoe did affect neither the numbers of CD11b + Ly6C high and CD11b - /Ly6C high osteoclast precursors (OCPs) in the BM of naïve mice nor their in vitro osteoclastogenic potential as indicated by comparable mRNA expression of osteoclast markers. Addition of oxLDL, but not LDL, to pre-osteoclasts from day 3 and mature osteoclasts from day 6 of osteoclastogenesis strongly reduced the number of TRAP + osteoclasts and their resorptive capacity. This coincided with a decreased expression of various osteoclast markers. Interestingly, oxLDL significantly lowered the expression of osteoclast-associated receptor (Oscar) and the DNAX adaptor protein-12 encoding gene Tyrobp, which regulate the immunoreceptor tyrosine-based activation motif (ITAM) co-stimulation pathway that is strongly involved in osteoclastogenesis. Collectively, our findings suggest that under inflammatory conditions in the joint, high LDL levels lessen bone destruction during AIA, probably by formation of oxLDL that inhibits osteoclast formation and activity through modulation of the ITAM-signaling.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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