Bone is a dynamic organ which continuously undergoes remodeling throughout one's lifetime. Cellular production of reactive oxygen species (ROS) is essential for regulating bone homeostasis. Osteoclasts, multinucleated giant cells differentiated from macrophage lineage, are responsible for osteolytic bone conditions which are closely linked to ROS signaling pathways. In this study, an anti-ROS enzyme, peroxiredoxin 1 (Prdx1) was found to be expressed both in bone marrow macrophages and osteoclasts. Recombinant Prdx1 protein was found to dose-dependently inhibit ROS production and osteoclast differentiation. Mechanistically, Prdx1 protein also attenuated NFATc1 activation as well as the expression of C-Fos, V-ATPase-d2, Cathepsin K, and Integrin αV. Collectively, Prdx1 is a negative regulator on osteoclast formation via inhibiting RANKL-mediated ROS activity, thus suggesting its potential application for treating osteoclast related disorders.
Keyphrases
- bone loss
- reactive oxygen species
- cell death
- dna damage
- signaling pathway
- bone marrow
- induced apoptosis
- bone mineral density
- cell cycle arrest
- oxidative stress
- poor prognosis
- adipose tissue
- soft tissue
- binding protein
- transcription factor
- long non coding rna
- protein protein
- single cell
- postmenopausal women
- rare case
- endoplasmic reticulum