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Inflammation
Published in: Inflammation 4/2023

10-04-2023 | Osteoarthrosis | RESEARCH

Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling

Authors: Zhibo Liu, Shidong Hu, Jiangping Wu, Xiaolin Quan, Chen Shen, Zhi Li, Xin Yuan, Xiangwei Li, Chao Yu, Ting Wang, Xudong Yao, Xianding Sun, Mao Nie

Published in: Inflammation | Issue 4/2023

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Abstract

Dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) signaling is involved in the dynamic balance of catabolism and anabolism in articular chondrocytes. This study aimed to investigate the roles and mechanism of DYRK1A in the pathogenesis of osteoarthritis (OA). The expressions of DYRK1A and its downstream signal epidermal growth factor receptor (EGFR) were detected in the cartilage of adult wild-type mice with destabilized medial meniscus (DMM) and articular cartilage of patients with OA. We measured the progression of osteoarthritis in chondrocyte-specific knockout DYRK1A(DYRK1A-cKO) mice after DMM surgery. Knee cartilage was histologically scored and assessed the effects of DYRK1A deletion on chondrocyte catabolism and anabolism. The effect of inhibiting EGFR signaling in chondrocytes from DYRK1A-cKO mice was analyzed. Trauma-induced OA mice and OA patients showed downregulation of DYRK1A and EGFR signaling pathways. Conditional DYRK1A deletion aggravates DMM-induced cartilage degeneration, reduces the thickness of the superficial cartilage, and increases the number of hypertrophic chondrocytes. The expression of collagen type II, p-ERK, and aggrecan was also downregulated, and the expression of collagen type X was upregulated in the articular cartilage of these mice. Our findings suggest that DYRK1A delays the progression of knee osteoarthritis in mice, at least in part, by maintaining EGFR-ERK signaling in articular chondrocytes.
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Metadata
Title
Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling
Authors
Zhibo Liu
Shidong Hu
Jiangping Wu
Xiaolin Quan
Chen Shen
Zhi Li
Xin Yuan
Xiangwei Li
Chao Yu
Ting Wang
Xudong Yao
Xianding Sun
Mao Nie
Publication date
10-04-2023
Publisher
Springer US
Published in
Inflammation / Issue 4/2023
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01813-6

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