CD11b Deficiency Favors Cartilage Calcification via Increased Matrix Vesicles, Apoptosis, and Lysyl Oxidase Activity
-
Published:2023-06-05
Issue:11
Volume:24
Page:9776
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Bernabei Ilaria1ORCID, Hansen Uwe2, Ehirchiou Driss1ORCID, Brinckmann Jürgen3, Chobaz Veronique1, Busso Nathalie1, Nasi Sonia1ORCID
Affiliation:
1. Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland 2. Institute for Musculoskeletal Medicine, University Hospital of Münster, 48149 Münster, Germany 3. Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany
Abstract
Pathological cartilage calcification is a hallmark feature of osteoarthritis, a common degenerative joint disease, characterized by cartilage damage, progressively causing pain and loss of movement. The integrin subunit CD11b was shown to play a protective role against cartilage calcification in a mouse model of surgery-induced OA. Here, we investigated the possible mechanism by which CD11b deficiency could favor cartilage calcification by using naïve mice. First, we found by transmission electron microscopy (TEM) that CD11b KO cartilage from young mice presented early calcification spots compared with WT. CD11b KO cartilage from old mice showed progression of calcification areas. Mechanistically, we found more calcification-competent matrix vesicles and more apoptosis in both cartilage and chondrocytes isolated from CD11b-deficient mice. Additionally, the extracellular matrix from cartilage lacking the integrin was dysregulated with increased collagen fibrils with smaller diameters. Moreover, we revealed by TEM that CD11b KO cartilage had increased expression of lysyl oxidase (LOX), the enzyme that catalyzes matrix crosslinks. We confirmed this in murine primary CD11b KO chondrocytes, where Lox gene expression and crosslinking activity were increased. Overall, our results suggest that CD11b integrin regulates cartilage calcification through reduced MV release, apoptosis, LOX activity, and matrix crosslinking. As such, CD11b activation might be a key pathway for maintaining cartilage integrity.
Funder
“Fonds National Suisse de la recherche scientifique”
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference45 articles.
1. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017;Disease;Lancet,2018 2. Calcification of articular cartilage in human osteoarthritis;Fuerst;Arthritis Rheum.,2009 3. Fuerst, M., Niggemeyer, O., Lammers, L., Schafer, F., Lohmann, C., and Ruther, W. (2009). Articular cartilage mineralization in osteoarthritis of the hip. BMC Musculoskelet. Disord., 10. 4. Articular cartilage calcification in osteoarthritis: Insights into crystal-induced stress;Ea;Arthritis Rheum.,2011 5. Cartilage calcification in osteoarthritis: Mechanisms and clinical relevance;Bernabei;Nat. Rev. Rheumatol.,2023
|
|