Information from the abstract
Iron overload disrupts bone homeostasis by suppressing osteoblast survival and mineralization, while promoting osteoclastogenesis. As a programmed cell death driven by iron-dependent lipid peroxidation and glutathione peroxidase 4 (GPX4) downregulation. This study investigated the role of ferroptosis in bone cells under iron overload. Exposure to ferric ammonium citrate (FAC) led to decreased osteoblast viability, downregulation of GPX4 and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and osteoblastic markers. It also increased ROS production and lipid peroxidation in osteoblasts. In addition, intracellular reduced glutathione (GSH) levels showed a decreasing trend in osteoblasts exposed to FAC. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly restored osteoblast viability and reduced lipid peroxidation, confirming the involvement of ferroptosis in iron-induced cytotoxicity. Additionally, iron overload increased the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, thereby promoting osteoclast differentiation. Interestingly, Fer-1 effectively attenuated these osteoclastogenic effects. On the other hand, FAC increased RAW264.7 osteoclast precursor cells viability, ROS production and lipid peroxidation; while, Fer-1 suppressed lipid peroxidation without affecting cell viability and ROS levels. Furthermore, we examined the role of cystine, an essential precursor for GSH synthesis and critical antioxidant cofactor for GPX4, in bone cells under iron-overload conditions. Cystine enhanced osteoblast viability and reduced osteoclast viability under iron overload, but it did not exhibit a synergistic effect with Fer-1. These findings highlight ferroptosis as an underlying mechanism for iron-induced osteoporosis and may represent a promising therapeutic strategy for managing iron overload-associated bone disorders.
Why this record is monitored
This record has an Impact Signal of 79/100 based on recency, source, collaboration, and bibliographic signals. It prioritizes monitoring and is not a judgment of research quality.
Related topics: Ferroptosis and cancer prognosis · Bone Metabolism and Diseases · Iron Metabolism and Disorders
Thai researcher and institutional participation
Supagarn Sooksawanwit · Kornkamon Lertsuwan · Natnicha Tannop · Ploypapus Lapatkeattisukul · Thanayuth Jenpichitkulchai · Nittiyaporn Sotapong · Jarinthorn Teerapornpuntakit · Tueanjai Khunluck · Siriwan Punvilai · Narattaphol Charoenphandhu · Mahidol University · Thammasat University · Chulabhorn Royal Academy
Data limitations
This page is a bibliographic record based on abstract-level information, not a full analysis or quality assessment. Verify the DOI and original article before citation.