Cyclovirobuxine Prevents Osteoclastogenesis and Estrogen Deficiency-Induced Bone Loss by Inhibiting ROS Generation via the PI3K/AKT/FOXO1 Pathway
TL;DR
The results suggest that CVB suppresses osteoclastogenesis and their resorptive function through modulation of MAPK and PI3K/AKT/FOXO1 pathways and by enhancing antioxidant defense, which has potential therapeutic value for antiosteoporosis treatment.
Abstract
This research investigates how CVB modulates osteoclast development and functional activity, and elucidates its underlying molecular mechanisms. Osteoclasts are pivotal mediators of bone matrix degradation and reconstruction, and their overactivation is an important mechanism in diseases such as osteoporosis. By extracting bone marrow-derived macrophages (BMMs) from mouse bone marrow and inducing them to differentiate into osteoclasts under RANKL and M-CSF stimulation, we found that CVB dose-dependently inhibited osteoclast differentiation, pseudopod structure formation, acid secretion and bone resorption function at nontoxic concentrations; inhibited PI3K/AKT pathway activation, enhanced the nuclear translocation and expression of FOXO1, and upregulated antioxidant enzymes such as CAT and SOD1, thereby suppressing intracellular ROS accumulation. Animal experiments further demonstrated that CVB exerted a protective effect against skeletal degradation in ovariectomized mice. These results suggest that CVB suppresses osteoclastogenesis and their resorptive function through modulation of MAPK and PI3K/AKT/FOXO1 pathways and by enhancing antioxidant defense, which has potential therapeutic value for antiosteoporosis treatment.