Role of the Interaction of Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors 1 and 2 in Bone-Related Cells

Hideki Kitaura, Aseel Marahleh, Fumitoshi Ohori, Takahiro Noguchi, Yasuhiko Nara, Adya Pramusita, Ria Kinjo, Jinghan Ma, Kayoko Kanou, Itaru Mizoguchi

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)


Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2). Bone is in a constant state of turnover; it is continuously degraded and built via the process of bone remodeling, which results from the regulated balance between bone-resorbing osteoclasts, bone-forming osteoblasts, and the mechanosensory cell type osteocytes. Precise interactions between these cells maintain skeletal homeostasis. Studies have shown that TNF-α affects bone-related cells via TNFRs. Signaling through either receptor results in different outcomes in different cell types as well as in the same cell type. This review summarizes and discusses current research on the TNF-α and TNFR interaction and its role in bone-related cells.

Original languageEnglish
Article number1481
JournalInternational journal of molecular sciences
Issue number3
Publication statusPublished - 2022 Feb 1


  • Osteoblast
  • Osteoclast
  • Osteocyte
  • TNF receptor-1
  • TNF receptor-2
  • TNF-α

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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