Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Abstract

AbstractOsteoclasts are cells primarily involved in bone remodeling. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration. However, given the limitations of current osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell‐free fat extract (CEFFE) is the liquid fraction obtained from adipose tissues, which are enriched with a variety of adipokines. This study aims to explore its pharmacologic effect on hyperactive osteoclastogenesis. CEFFE exhibits excellent potentials to attenuate osteoclast‐associated bone loss in ovariectomy mice and to inhibit osteoclastogenesis in primary monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE‐Cation) is identified as the main inhibitory component in osteoclast formation assay. According to liquid chromatography with tandem mass spectrometry analysis, the CEFFE‐Cation fraction mainly consists of various antioxidant enzymes and cytokines, which endow it with a superior antioxidant capacity. Meanwhile, CEFFE‐Cation is also capable of mitigating Ca2+ oscillation and subsequent nuclear factor of activated T‐cells 1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next‐generation personalized antiresorptive agent for osteolytic bone disease treatment.