Inhibitory molecular mechanisms of inflammatory and Hormonal deficiency- induced bone loss

Abstract

The Bone is a metabolically active organ that undergoes continuous remodeling to have a balanced homeostasis under physiological condition. Tipped balance induces impaired bone metabolism. Excessive bone resorption results in bone loss. We set two animal models for bone loss induced by inflammation and estrogen deficiency. Lipopolysaccharides (LPS) had been injected in mice to induce inflammatory bone loss. Dauricine (DAC), an isoquinoline alkaloid protected from LPS- induced bone loss. DAC reduced the differentiation and activity of osteoclasts by decreasing ROS via the ROS/PP2A/NF-Kb axis. These results implied the therapeutic potential of DAC against inflammatory bone loss. In ovariectomy (OVX)- induced bone loss, Estrogen (E2) decreased the bone loss. E2 decreased the size of osteoclasts via blocking a signal for actin ring formation without affecting differentiation. E2 binding to estrogen receptor (ERα) forms a complex with SHP2/c-Src to decrease c-Src activation that was induced upon RANKL stimulation in a non-genomic manner, leading to impaired cytoskeletal organization of osteoclasts and reducing bone resorption.