In vitro and in vivo investigations on arsenic-induced cartilage degeneration in osteoarthritis

• Published in: Journal of hazardous materials Vol. 461; p. 132570
• Main Authors: Suminda, Godagama Gamaarachchige Dinesh, Min, Yunhui, Ha, Min Woo, Ghosh, Mrinmoy, Lee, Dong-Sun, Son, Young-Ok
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.01.2024
• Subjects: Arsenic; Cartilage degeneration; Osteoarthritis; Reactive oxygen species; Cartilage degeneration; Reactive oxygen species; Arsenic; HRP; Rot/AA; FCCP; MTT; DMEM; NF-κB; CCCP; OA; IA; WT; WHO; AQP; DMM; H&E; OARSI; NAC; ROS; ICP-MS; PM; Osteoarthritis; JC-1; OCR
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2023.132570

Heavy metals found in the environment, including arsenic (As) pose significant risks to human health and present a risk factor for osteoarthritis (OA). This study researched the impact of As on cartilage degeneration by focusing on the role of As in causing OA in mice. We employed chemical inhibition and inductively coupled plasma mass spectrometry analyses to identify the effect of As on chondrocytes as well as studying its accumulation in organs after oral administration in mice. Additionally, the study examined the effect of intra-articular As treatment on the levels of crucial catabolic factors, namely Hif-2α (Epas1) and Zip8 (Slc39a8), during OA progression. Mice that were administered As orally in conjunction with surgically induced joint instability, had heightened cartilage destruction compared to wild-type mice. Quantitative analysis revealed a significant increase in Hif-2α and Zip8 mRNA expression (p = 0.0352,0.0004 respectively) and protein expression (p = 0.0101,0.008 respectively) post oral administration. Our findings illustrated the role of As in influencing crucial cellular functions that are triggered by reactive oxygen species. These events consequently activate the Akt/Hif-2α/NF-κB pathways, leading to disruptions in articular cartilage homeostasis. This study provides a comprehensive understanding of the impact of As on the development of osteoarthritis. [Display omitted] •Arsenic (As) induces disruption of redox homeostasis in chondrocytes.•Consumption of As-contaminated water leads to As accumulation in the knee joints.•As accelerated both early onset OA symptoms and post-injury OA.•Hif-2α/Zip8 were involved in this process.•As-induced ROS release upregulates Hif-2α/Zip8 transcriptional activation.