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

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

作者地址："[Liu, Zhibo; Hu, Shidong; Wu, Jiangping; Quan, Xiaolin; Shen, Chen; Li, Zhi; Yuan, Xin; Li, Xiangwei; Wang, Ting; Yao, Xudong; Sun, Xianding; Nie, Mao] Chongqing Med Univ, Ctr Joint Surg, Dept Orthoped Surg, Affiliated Hosp 2, Yuzhong Dist, 76 Linjiang Rd, Chongqing, Peoples R China; [Yu, Chao] Chongqing Med Univ, University Town Hosp, Dept Orthopaed Surg, Chongqing, Peoples R China"

通信作者："Nie, M (通讯作者)，Chongqing Med Univ, Ctr Joint Surg, Dept Orthoped Surg, Affiliated Hosp 2, Yuzhong Dist, 76 Linjiang Rd, Chongqing, Peoples R China."

来源：INFLAMMATION

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000966939600002

JCR分区：Q2

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：osteoarthritis; DYRK1A; EGFR; ERK; catabolism; anabolism

摘要："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."

基金机构：Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0806]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University

基金资助正文："This paper was partially supported by grants from the Natural Science Foundation of Chongqing (no. cstc2020jcyj-msxmX0806, Ting Wang) and Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (Mao Nie)."