Monoamine oxidase A attenuates chondrocyte loss and extracellular matrix degradation in osteoarthritis by inducing autophagy.

Ming Li, Zhibin Peng, Xiaokun Wang, Yansong Wang

International immunopharmacology 2022 Aug

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Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage destruction and extracellular matrix (ECM) degeneration. Here, we studied the potential function of monoamine oxidase A (MAOA) in OA pathogenesis. Cartilage tissue samples were collected from 33 patients with knee OA and nine normal healthy controls. Sprague-Dawley rats with anterior cruciate ligament transection (ACLT) and primary chondrocytes treated with interleukin (IL)-1β were used as OA animal and cell models, respectively. The effects of adenovirus-mediated MAOA overexpression in OA models were studied using Safranin-O staining, immunohistochemistry, CCK-8 assay, EdU assay, flow cytometry, qRT-PCR, western blotting, and immunofluorescence. MAOA was identified as an overlapping downregulating gene in the GSE82107, GSE1919, GSE169077, and GSE29746 datasets. MAOA expression was negatively correlated with OA severity. MAOA downregulation was confirmed in ACLT rats and IL-1β-treated chondrocytes. Notably, MAOA overexpression significantly inhibited ACLT-induced OA pathogenesis in rats, as was evidenced by the reduced Osteoarthritis Research Society International (OARSI) score and serum crosslinked C-telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP) levels. These findings show that MAOA overexpression inhibits extracellular matrix (ECM) degradation and promotes ACLT-induced autophagy. The effects of MAOA on ECM degradation and autophagy were also confirmed in IL-1β-treated primary chondrocytes. Additionally, MAOA protects chondrocytes against IL-1β-induced apoptosis. Furthermore, treating chondrocytes with 3-MA significantly attenuated the protective effects of MAOA. MAOA was identified as a downregulated gene in OA. Restoring MAOA expression protects against chondrocyte loss and ECM degradation through autophagy regulation. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Ming Li, Zhibin Peng, Xiaokun Wang, Yansong Wang. Monoamine oxidase A attenuates chondrocyte loss and extracellular matrix degradation in osteoarthritis by inducing autophagy. International immunopharmacology. 2022 Aug;109:108772