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

Geng,Yuan‑Ming; Liu,Cheng‑Xia; Lu,Wei‑Ying; Liu,Ping; Yuan,Pei‑Yan; Liu,Wei‑Long; Xu,Ping‑Ping; Shen,Xiao‑Qing

doi:10.3892/mmr.2019.10688

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

Authors:
- Yuan‑Ming Geng
- Cheng‑Xia Liu
- Wei‑Ying Lu
- Ping Liu
- Pei‑Yan Yuan
- Wei‑Long Liu
- Ping‑Ping Xu
- Xiao‑Qing Shen
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Affiliations: Department of Stomatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
Published online on: September 16, 2019 https://doi.org/10.3892/mmr.2019.10688
Pages: 4193-4201
Copyright: © Geng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role of lysosomal‑associated transmembrane protein 5 (LAPTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LAPTM5 were downregulated following runt‑related transcription factor 2 (RUNX2) silencing and upregulated following RUNX2 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 (RANKL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LAPTM5 silencing in ST2 cells enhanced osteoclastic differentiation of co‑cultured RAW264.7 cells. The present study indicated that expression of LAPTM5 was regulated by the interaction of RUNX2 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 RUNX2 may be involved in osteoclast differentiation through the regulation of the lysosome‑associated genes that modulate RANKL expression.

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