Inhibiting Lysyl Oxidases prevents pathologic cartilage calcification.

Autor: Bernabei I; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Faure E; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Romani M; Aging and Bone Metabolism Laboratory, Service of Geriatric Medicine & Geriatric Rehabilitation, Department of Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Wegrzyn J; Department of Orthopedic Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Brinckmann J; Department of Dermatology and Institute of Virology and Cell Biology, University of Lübeck, Lübeck, Germany., Chobaz V; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., So A; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Hugle T; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Busso N; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland., Nasi S; Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland. Electronic address: sonia.nasi@chuv.ch.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Feb; Vol. 171, pp. 116075. Date of Electronic Publication: 2024 Jan 05.
DOI: 10.1016/j.biopha.2023.116075
Abstrakt: Lysyl oxidases (LOX(L)) are enzymes that catalyze the formation of cross-links in collagen and elastin fibers during physiologic calcification of bone. However, it remains unknown whether they may promote pathologic calcification of articular cartilage, an important hallmark of debilitating arthropathies. Here, we have studied the possible roles of LOX(L) in cartilage calcification, related and not related to their cross-linking activity. We first demonstrated that inhibition of LOX(L) by β-aminoproprionitrile (BAPN) significantly reduced calcification in murine and human chondrocytes, and in joint of meniscectomized mice. These BAPN's effects on calcification were accounted for by different LOX(L) roles. Firstly, reduced LOX(L)-mediated extracellular matrix cross-links downregulated Anx5, Pit1 and Pit2 calcification genes. Secondly, BAPN reduced collagen fibrotic markers Col1 and Col3. Additionally, LOX(L) inhibition blocked chondrocytes hypertrophic differentiation (Runx2 and COL10), pro-inflammatory IL-6 release and reactive oxygen species (ROS) production, all triggers of chondrocyte calcification. Through unbiased transcriptomic analysis we confirmed a positive correlation between LOX(L) genes and genes for calcification, hypertrophy and extracellular matrix catabolism. This association was conserved throughout species (mouse, human) and tissues that can undergo pathologic calcification (kidney, arteries, skin). Overall, LOX(L) play a critical role in the process of chondrocyte calcification and may be therapeutic targets to treat cartilage calcification in arthropathies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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