Transmembrane protein 173 inhibits RANKL-induced osteoclast differentiation

FEBS Lett. 2015 Mar 24;589(7):836-41. doi: 10.1016/j.febslet.2015.02.018. Epub 2015 Feb 26.

Abstract

Tmem173 was identified as a growth inhibitor associated with major histocompatibility complex (MHC) class II and a potential stimulator for IFN-β, an innate immune inducer and a negative feedback controller for RANKL-induced osteoclast differentiation of monocytic macrophage cells. In this study, we confirmed that transmembrane protein 173 (Tmem173) overexpression inhibited the expression of osteoclast-specific genes, tartrate-resistant acid phosphatase (TRAP), cathepsin K, and matrix metalloproteinase-9 (MMP-9), as well as bone resorption pit formation in RANKL-treated RAW 264.7 cells. Activation of osteoclast-specific transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic-1 (NFATc1), and RANKL-induced activation of ERK were also down-regulated by Tmem173 overexpression. Collectively, these results suggest that Tmem173 plays a regulatory role in RANKL-RANK-mediated signaling in osteoclastogenesis.

Keywords: Osteoclastogenesis; RANK ligand; Tartrate-resistant acid phosphatase; Transmembrane protein 173.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Osteoprotegerin / metabolism
  • RANK Ligand / genetics
  • RANK Ligand / metabolism*
  • Signal Transduction

Substances

  • Membrane Proteins
  • Osteoprotegerin
  • RANK Ligand
  • Sting1 protein, mouse
  • Tnfsf11 protein, mouse