Intracellular fragmentation of bone resorption products by reactive oxygenspecies generated by osteoclastic tartrate-resistant acid phosphatase

Tartrate-resistant acid phosphatase (TRAP) is highly expressed in bone-reso rbing osteoclasts and activated macrophages, It has been suggested that a r edox-active iron in the binuclear iron center of TRAP could have the capaci ty to react with hydrogen peroxide to produce highly destructive reactive o xygen species (ROS), Here we show that TRAP can generate ROS in vitro and t hat cells over-expressing TRAP produce higher amounts of intracellular ROS than their parent cells. We further demonstrate that these ROS can be targe ted to destroy collagen and other proteins. In resorbing osteoclasts, TRAP was found in transcytotic vesicles transporting matrix degradation products through the cell, suggesting that TRAP-facilitated fragmentation of endocy tosed material takes place in a specific cellular compartment. These result s suggest that bone matrix degradation occurs not only extracellularly in t he resorption lacunae but also intracellularly in the transcytotic vesicles . We propose that proteins containing redox-active iron could represent a n ovel mechanism of physiological fragmentation of organic molecules. This me chanism could be important in tissue remodeling and as a defense mechanism of phagocytosing cells.