Lipopolysaccharide inhibits osteoblast formation and receptor activator of nuclear factor-κB ligand degradation via autophagy inhibition.

Abstract

Lipopolysaccharide (LPS) and Receptor Activator of Nuclear Factor-κB Ligand (RANKL) are the two important factors causing bone loss, which is an important pathogenesis for osteoporosis. However, the relationship between LPS and RANKL is not yet clear. LPS can be involved in the weakened osteoblast formation as an autophagy regulator, and osteoblasts and their precursors are the source cells for RANKL production. Our study aimed to explore the relationship between autophagy changes and RANKL production during LPS-regulated osteoblasts. Our results showed that LPS inhibited autophagy (LC3 conversion and autophagosome formation) and enhanced the protein and mRNA expression of RANKL in MC3T3-E1 osteoblast precursor line. Autophagy upregulation with Rapamycin over BECN1 overexpression rescued LPS-inhibited osteoblast formation and -promoted RANKL protein production in MC3T3-E1 cells. In vivo experiments supported that damaged bone mass, bone microstructure, osteoblastic activity (ALP and P1NP production by ELISA assays) and enhanced RANKL production by LPS administration were partially rescued by Rapamycin application. In conclusion, LPS can inhibit autophagy in osteoblast precursors, thereby inhibiting osteoblast formation and RANKL autophagic degradation.