Colony-stimulating factor 1 receptor inhibition prevents against lipopolysaccharide -induced osteoporosis by inhibiting osteoclast formation

Abstract Lipopolysaccharide (LPS) can induce bone loss by stimulating osteoclast formation. Colony-stimulating factor 1 receptor (CSF 1R) inhibitors have great potential for the treatment of rheumatoid arthritis and tumor-related bone erosion. However, its role in LPS-induced bone loss is still not clarified. In this study, we observed the effects of CSF 1R inhibitor, PLX3397, on LPS-induced bone damage in an animal model. The models were established by LPS administration in male Sprague-Dawley rats. PLX3397 (30 mg/kg body weight) was given by oral gavage. MicroCT analysis, biomechanical properties, biomarker assay, histological examination, and mRNA expression of osteoclast differentiation-related genes (Traf6, Fra1, c-fos and NFATc1) were performed on the 8th week. LPS induced bone loss was shown as the decrease in bone volume fraction and trabecular number and increase in trabecular separation (p