FTH1 protects against osteoarthritis by inhibits ECM degradation via the MAPK pathway

Abstract Ferritin heavy chain 1, which FTH codes, is an important subunit of ferro-storing proteins and is indispensable in iron metabolism. It has been extensively researched in numerous organs and illnesses. Nevertheless, the relationship between FTH1 and osteoarthritis (OA) remains unclear. Here, we highlighted the significance of FTH1 in the pathophysiology of OA and identified it as a critical mediator of chondrocyte senescence and extracellular matrix(ECM) degradation. We discovered that FTH1 expression was downregulated in OA patients as well as mice after destabilized medial meniscus surgery (DMM). Knocking down of FTH1 caused articular cartilage damage and extracellular matrix degradation in cartilage explants. Furthermore, increased FTH1 expression can lessen the susceptibility of chondrocytes to ferroptosis, and reversed the decreased of SOX9 and aggrecan after DMM surgery in mice. The further study demonstrated that FTH1 relieved osteoarthritis by inhibiting the MAPK pathway in chondrocytes. Our study proved that FTH1 played an essential role in extracellular matrix degradation, ferroptosis and chondrocytes senescence during OA procedure, and intra-injection of adenovirus expressing FTH1 perhaps a viable and potential strategy for OA prevention and therapy.