Interleukin-7 Induces Osteoclast Formation via STAT5, Independent of Receptor Activator of NF-kappaB Ligand. Academic Article uri icon

Overview

abstract

  • Interleukin-7 (IL-7), which is required for the development and survival of T cells in the thymus and periphery, plays a role in joint destruction. However, it remains unclear how IL-7 affects osteoclast formation. Thus, we investigated the mechanism by which IL-7 induced osteoclast formation through IL-7 receptor α (IL-7Rα) in osteoclast precursors. We cultured peripheral blood mononuclear cells or synovial fluid mononuclear cells with IL-7 in the presence or absence of an appropriate inhibitor to analyze osteoclast formation. We also constructed IL-7Rα-expressing RAW264.7 cells to uncover the mechanism(s) by which IL-7 induced osteoclast formation differed from that of receptor activator of nuclear factor κB ligand (RANKL). We found that IL-7 induced osteoclast formation of human monocytes from peripheral blood or synovial fluid in a RANKL-independent and a signal transducer and activator of transcription 5 (STAT5)-dependent manner. IL-7-induced osteoclasts had unique characteristics, such as small, multinucleated tartrate-resistant acid phosphatase positive cells and no alterations even when RANKL was added after IL-7 pretreatment. RAW264.7 cells, if overexpressing IL-7Rα, also were able to differentiate into osteoclasts by IL-7 through a STAT5 signaling pathway. Furthermore, IL-7-induced osteoclast formation was repressed by inhibitors of the IL-7R signaling molecules Janus kinase and STAT5. Our findings demonstrate that IL-7 is a truly osteoclastogenic factor, which may induce osteoclast formation via activation of STAT5, independent of RANKL. We also suggest the possibility that an IL-7R pathway blocker could alleviate joint damage by inhibiting osteoclast formation, especially in inflammatory conditions.

authors

  • Kim, Jin-Hee
  • Sim, Jihyun
  • Lee, Sunkyung
  • Seol, Min A
  • Ye, Sang-Kyu
  • Shin, Hyun Mu
  • Lee, Eun Bong
  • Lee, Yun Jong
  • Choi, Yun Jung
  • Yoo, Wan-Hee
  • Kim, Jin Hyun
  • Kim, Wan-Uk
  • Lee, Dong-Sup
  • Kim, Jin-Hong
  • Kang, Insoo
  • Kang, Seong Wook
  • Kim, Hang-Rae

publication date

  • October 20, 2017

Identity

PubMed Central ID

  • PMC5655015

Scopus Document Identifier

  • 84892491195

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2017.01376

PubMed ID

  • 29104576

Additional Document Info

volume

  • 8