Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Abstract

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species (ROS) emerges as a viable approach in addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly those derived from lentinan (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of RANKL-induced osteoclastogenesis and osteoclastic activity when compared to alternative Se species. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over macrophage polarization, osteoclast activity inhibition, and the prevention of CIA/OVX-induced osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1 to re-polarize macrophages. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders, with considerable potential for clinical translation. This article is protected by copyright. All rights reserved.