Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobalt-chromium-molybdenum (CoCrMo) particles-induced tumor necrosis factor-α (TNFα) secretion in MLO-Y4 osteocytes

Vbenosawemwinghaye Orhue, Arihiko Kanaji, Marco S. Caicedo, Amarjit S. Virdi, Dale R. Sumner, Nadim J. Hallab, Holger Jahr, Kotaro Sena

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aseptic loosening is the devastating long term complication of total hip arthroplasty and orthopedic implant debris has been shown to trigger an intense inflammatory reaction leading to resorption of the bone matrix. Inflammatory cytokines, such as tumor necrosis factor-α (TNFα), have been implicated in this process and osteocytes may play a role in its production. We previously demonstrated that cobalt-chromium-molybdenum (CoCrMo) particles upregulate TNFα production by MLO-Y4 osteocytes in vitro, but the underlying mechanism has not been elucidated. Based on previous studies by others, we hypothesized that the calcineurin-nuclear factor of activated T cells (NFAT) pathway mediates CoCrMo particle-induced TNFα production in MLO-Y4 osteocytes. MLO-Y4 osteocytes exposed to CoCrMo particle treatment resulted in a rapid and significant increase in calcineurin activity. We also demonstrate that CoCrMo particle-induced upregulation of TNFα is reduced to control levels with calcineurin-NFAT inhibitors and this was also confirmed at mRNA level. Moreover, we demonstrate the localization of NFATs in MLO-Y4 osteocytes and that NFAT1 and 2 translocate to the nucleus upon CoCrMo particle treatment. Our results suggest that calcineurin-NFAT signaling is involved in TNFα production by MLO-Y4 osteocytes after CoCrMo particle treatment.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalJournal of Orthopaedic Research
Volume29
Issue number12
DOIs
Publication statusPublished - 2011 Dec
Externally publishedYes

Fingerprint

NFATC Transcription Factors
Osteocytes
Molybdenum
Calcineurin
Chromium
Cobalt
Tumor Necrosis Factor-alpha
Up-Regulation
Bone Matrix
Arthroplasty
Orthopedics
Hip
Therapeutics
Cytokines
Messenger RNA

Keywords

  • calcineurin
  • CoCrMo particles
  • MLO-Y4 osteocytes
  • nuclear factor of activated T cells (NFAT)
  • tumor necrosis factor-α (TNFα)

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobalt-chromium-molybdenum (CoCrMo) particles-induced tumor necrosis factor-α (TNFα) secretion in MLO-Y4 osteocytes. / Orhue, Vbenosawemwinghaye; Kanaji, Arihiko; Caicedo, Marco S.; Virdi, Amarjit S.; Sumner, Dale R.; Hallab, Nadim J.; Jahr, Holger; Sena, Kotaro.

In: Journal of Orthopaedic Research, Vol. 29, No. 12, 12.2011, p. 1867-1873.

Research output: Contribution to journalArticle

Orhue, Vbenosawemwinghaye ; Kanaji, Arihiko ; Caicedo, Marco S. ; Virdi, Amarjit S. ; Sumner, Dale R. ; Hallab, Nadim J. ; Jahr, Holger ; Sena, Kotaro. / Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobalt-chromium-molybdenum (CoCrMo) particles-induced tumor necrosis factor-α (TNFα) secretion in MLO-Y4 osteocytes. In: Journal of Orthopaedic Research. 2011 ; Vol. 29, No. 12. pp. 1867-1873.
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