LAPTM5 is transactivated by RUNX2 and involved in RANKL trafficking in osteoblastic cells

Abstract

The present study aimed to investigate the role of lysosomal-associated transmembrane protein 5 (LA PTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LA PTM5 were downregulated following runt-related transcription factor 2 (RUN X2) silencing and upregulated following RUN X2 overexpression in ST2 cells. Chromatin immunoprecipitation analysis identified the binding of RUNX2 to the LAPTM5 promoter at the -1176 to -1171 position. Dual-luciferase reporter assays confirmed that RUNX2 directly activated the LAPTM5 gene. The concentration of receptor activator of nuclear factor-κB ligand (RAN KL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LA PTM5 silencing in ST2 cells enhanced osteoclastic differentiation of co-cultured RA W264.7 cells. The present study indicated that expression of LA PTM5 was regulated by the interaction of RUN X2 with its promoter region and that LAPTM5 was involved in the trafficking of RANKL. These findings suggested a possible coupling mechanism between osteogenesis and osteoclastogenesis in which RUN X2 may be involved in osteoclast differentiation through the regulation of the lysosome-associated genes that modulate RAN KL expression.