Deletion of DYRK1A accelerates osteoarthritis progression through suppression of EGFR-ERK signaling

Abstract

Purpose 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). Methods 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. Results Trauma-induced OA mice and OA patients showed down-regulation 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 down-regulated, and the expression of collagen type X was up-regulated in the articular cartilage of these mice. Conclusion 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.

Platelet-Derived Exosomes Alleviate Knee Osteoarthritis by Attenuating Cartilage Degeneration and Subchondral Bone Loss

“…DYRK1A has been proven to improve symptoms of knee OA through increasing anabolism, decreasing catabolism, and enhancing chondrogenesis, chondrocyte function, and anti-inflammation. 7,24 AMD1 and TMEM30 could promote cell proliferation and migration in a variety of cell types. 22,52,53 Although a considerable number of lncRNAs in Plt-exos have been reported, few have been characterized for their function and mechanism.…”