TNF-α and RANKL promote osteoclastogenesis by upregulating RANK via the NF-κB pathway

Gang Luo, Fangfei Li, Xiaoming Li, Zheng Guo Wang, Bo Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

104 Citations (Scopus)


Although tumor necrosis factor alpha (TNF-α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF-α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF-α influences osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand (RANKL) with or without TNF-α for 4 days. Then, NF-κB was inhibited using the inhibitor, BAY 11-7082. The results indicated that treatment with TNF-α alone did not induce osteoclastogenesis of BMMs. However, TNF-α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11-7082 prevented the formation of mature osteoclasts by BMMs treated with TNF-α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF-α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF-κB pathway may serve an important role in this process.

Original languageEnglish
Pages (from-to)6605-6611
Number of pages7
JournalMolecular Medicine Reports
Issue number5
Publication statusPublished - May 2018

Scopus Subject Areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

User-Defined Keywords

  • Nuclear factor-κB
  • Osteoclast
  • Receptor activator of nuclear factor-κB
  • Tumor necrosis factor α


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