The Effects and Mechanisms of Chrysosplenetin in Targeting RANKL‐Induced NF‐κB Signaling and NFATc1 Activation to Protect Bone Density in Osteolytic Diseases

Abstract

Chrysosplenetin (CHR), an O‐methylated flavonol from Chamomilla recutita and Laggera pterodonta, has previously demonstrated efficacy in enhancing osteoblast differentiation for treating postmenopausal osteoporosis. This study aims to evaluate CHR's potential to inhibit osteoclastogenesis and prevent bone deterioration in both in vitro and in vivo models. Using tartaric acid‐resistant acid phosphatase staining and hydroxyapatite resorption assays, we examined the impact of CHR on RANKL‐induced osteoclasts derived from mouse bone marrow monocytes. Additionally, Western blot analysis and qRT‐PCR were utilized to assess the protein and gene expressions within the MAPK and NF‐κB signaling pathways, as well as the NFATc1 pathway. In vivo, CHR's effects were validated using micro‐CT and histomorphometry in an ovariectomized mouse model, showing significant reduction in osteoclast activity and bone loss. The study confirms CHR's inhibition of osteoclastogenesis through interference with RANKL‐mediated signaling pathways, suggesting its potential as a novel therapeutic agent for osteolytic conditions related to osteoclast‐osteoblast dysregulation.