IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex

Ichiro Nakamura, Yuho Kadono, Hiroshi Takayanagi, Eijiro Jimi, Tsuyoshi Miyazaki, Hiromi Oda, Kozo Nakamura, Sakae Tanaka, Gideon A. Rodan, Le T. Duong

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Targeted disruption of either c-Src or TNFR-associated factor 6 (TRAF6) in mice causes osteoclast dysfunction and an osteopetrotic phenotype, suggesting that both molecules play important roles in osteoclastic bone resorption. We previously demonstrated that IL-1 induces actin ring formation and osteoclast activation. In this study, we examined the relationship between IL-1/TRAF6- dependent and c-Src-mediated pathways in the activation of osteoclast-like cells (prefusion cells (pOCs); multinucleated cells) formed in the murine coculture system. In normal pOCs, IL-1 induces actin ring formation and tyrosine phosphorylation of p130Cas, a known substrate of c-Src. However, in Src-deficient pOCs, p130Cas was not tyrosine phosphorylated following IL-1 treatment. In normal pOCs treated with IL-1, anti-TRAF6 Abs coprecipitate p130Cas, protein tyrosine kinase 2, and c-Src. In Src-deficient pOCs, this molecular complex was not detected, suggesting that c-Src is required for formation of the TRAF6, p130Cas, and protein tyrosine kinase 2 complex. Moreover, an immunocytochemical analysis revealed that in osteoclast-like multinucleated cells, IL-1 induced redistribution of TRAF6 to actin ring structures formed at the cell periphery, where TRAF6 also colocalized with c-Src. Taken together, these data suggest that IL-1 signals feed into the tyrosine kinase pathways through a TRAF6-Src molecular complex, which regulates the cytoskeletal reorganization essential for osteoclast activation.

Original languageEnglish
Pages (from-to)5103-5109
Number of pages7
JournalJournal of Immunology
Volume168
Issue number10
DOIs
Publication statusPublished - May 15 2002
Externally publishedYes

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TNF Receptor-Associated Factor 6
Osteoclasts
Interleukin-1
Focal Adhesion Kinase 1
Crk-Associated Substrate Protein
Actins
Tyrosine
Bone Resorption
Coculture Techniques
Protein-Tyrosine Kinases
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex. / Nakamura, Ichiro; Kadono, Yuho; Takayanagi, Hiroshi; Jimi, Eijiro; Miyazaki, Tsuyoshi; Oda, Hiromi; Nakamura, Kozo; Tanaka, Sakae; Rodan, Gideon A.; Duong, Le T.

In: Journal of Immunology, Vol. 168, No. 10, 15.05.2002, p. 5103-5109.

Research output: Contribution to journalArticle

Nakamura, I, Kadono, Y, Takayanagi, H, Jimi, E, Miyazaki, T, Oda, H, Nakamura, K, Tanaka, S, Rodan, GA & Duong, LT 2002, 'IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex', Journal of Immunology, vol. 168, no. 10, pp. 5103-5109. https://doi.org/10.4049/jimmunol.168.10.5103
Nakamura, Ichiro ; Kadono, Yuho ; Takayanagi, Hiroshi ; Jimi, Eijiro ; Miyazaki, Tsuyoshi ; Oda, Hiromi ; Nakamura, Kozo ; Tanaka, Sakae ; Rodan, Gideon A. ; Duong, Le T. / IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex. In: Journal of Immunology. 2002 ; Vol. 168, No. 10. pp. 5103-5109.
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