Anti-inflammatory capacity of Apremilast in human chondrocytes is dependent on SOX-9
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Inflammation Research
ORIGINAL RESEARCH PAPER
Anti‑inflammatory capacity of Apremilast in human chondrocytes is dependent on SOX‑9 Yanjie Zhang1 · Xiaohan Huang1 · Yanhao Yuan1 Received: 13 June 2020 / Revised: 28 July 2020 / Accepted: 8 August 2020 © Springer Nature Switzerland AG 2020
Abstract Background and purpose Osteoarthritis (OA) impacts the quality of life in middle-aged and elderly people by inducing immobility. The severe inflammation in chondrocytes is reported to be related to the development and process of OA. The present study aims to investigate the protective effects of Apremilast on injured chondrocytes induced by interleukin-1α (IL-1α) and the underlying mechanism. Methods 10 ng/mL IL-1α was used to induce the in vitro injured chondrocytes. QRT-PCR was used to evaluate the expression level of Sry-type high-mobility-group box 9 (SOX-9), collagen type II alpha-1 gene (COL2A1), Aggrecan (ACAN) and collagen type X alpha 1 chain (COL10A1). SiRNA technology was utilized to knock down the expression of SOX-9 in the chondrocytes. The expression of SOX-9 was determined by Western Blot assay and/or immunofluorescence assay. Western Blot was used to evaluate the expression level of phosphorylated cyclic AMP response element binding (CREB). Results SOX9, Col2a1 and Acan were significantly up-regulated and Col10a1 was significantly down-regulated in the chondrocytes by Apremilast in a dose-dependent manner. IL-1α induced the injured chondrocytes by decreasing the expression of SOX9, Col2a1, Acan and increasing the expression of Col10a1, which were greatly reversed by Apremilast. By silencing SOX-9, the effects of Apremilast on SOX9 and marker genes were abolished. Phosphorylated CREB was up-regulated by Apremilast in a time-dependent manner. The up-regulated SOX-9 by Apremilast was reversed by the protein kinase A (PKA)/CREB pathway inhibitor H89. Conclusion Apremilast may protect chondrocytes from inflammation by up-regulating SOX9. Keywords Apremilast · Chondrocytes · SOX-9 · Osteoarthritis · CREB
Introduction Osteoarthritis (OA) is a common joint disease that presents articular cartilage degeneration, hyperplasia on articular bone margin and subchondral bone as classic clinical symptoms [1, 2]. Most OA patients are over the age of 50 and OA severely impacts the quality of life in middle-aged and elderly people. The main effects of OA are focused on the joints with high weight bearing or physical frequency, Responsible Editor: John Di Battista. * Yanjie Zhang [email protected] 1
Department of Orthopaedics, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), No. 82 South Qi Ming Road, Luoyang 471002, Henan, China
such as knee, hip, and ankle joints. The normal biological function of cartilage tissue, synovial tissue, subchondral bone, and periarticular muscle tissue will be affected [3, 4]. The dysfunction of joints in OA patients will be induced by pathological changes such as the depletion in numbers of chondrocytes, the metabolic unbalance of extracellula
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