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

Abstract

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.

• Authors: Gang Luo, Fangfei Li, Xiaoming Li, Zheng-Guo Wang, Bo Zhang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 17 Issue 5 Pg. 6605-6611 (05 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 29512766 (Publication Type: Journal Article)

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• NF-kappa B
• Nitriles
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Sulfones
• Tnfrsf11a protein, mouse
• Tnfsf11 protein, mouse
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cell Differentiation
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitriles (pharmacology)
• Osteoclasts (cytology, metabolism)
• RANK Ligand (metabolism)
• Receptor Activator of Nuclear Factor-kappa B (metabolism)
• Sulfones (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)