Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration.

Abstract

Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload‑induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload‑induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro, followed by co‑treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA‑AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co‑treatment with BAPTA‑AM. Moreover, BAPTA‑AM suppressed iron influx into chondrocytes and inhibited iron overload‑induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism‑related diseases and iron overload‑induced OA progression.

• Authors: Xingzhi Jing, Qiang Wang, Ting Du, Weimin Zhang, Xiaoyang Liu, Qiang Liu, Tao Li, Guodong Wang, Feifei Chen, Xingang Cui
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 48 Issue 4 (10 2021) ISSN: 1791-244X [Electronic] Greece
• PMID: 34468013 (Publication Type: Journal Article)

Chemical References

• Calcium Chelating Agents
• Ferric Compounds
• Protective Agents
• Quaternary Ammonium Compounds
• Reactive Oxygen Species
• 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
• Egtazic Acid
• ferric ammonium citrate

Topics

• Animals
• Apoptosis (drug effects)
• Calcium Chelating Agents (pharmacology)
• Cartilage Diseases (drug therapy, metabolism)
• Cartilage, Articular (drug effects, metabolism)
• Cell Survival (drug effects)
• Cells, Cultured
• Chondrocytes (drug effects, metabolism)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Ferric Compounds (pharmacology)
• Iron Overload (complications, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism)
• Mitochondrial Diseases (chemically induced, drug therapy, metabolism)
• Osteoarthritis (drug therapy, metabolism)
• Protective Agents (pharmacology)
• Quaternary Ammonium Compounds (pharmacology)
• Reactive Oxygen Species (metabolism)