Effect of celecoxib on Ca2+ movement and cell proliferation in human osteoblasts

Jue L. Wang, Ko L. Lin, Jin S. Chen, Yih C. Lu, Bang P. Jiann, Hong T. Chang, Shu S. Hsu, Wei C. Chen, Jong K. Huang, Chin M. Ho, Chung R. Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

25 Scopus citations

Abstract

In human osteoblasts, the effect of the widely prescribed cyclooxygenase-2 inhibitor celecoxib on intracellular Ca2+ concentrations ([Ca 2+]i) and cell proliferation was explored by using fura-2 and the tetrazolium assay, respectively. Celecoxib at concentrations greater than 1μM caused a rapid rise in [Ca2+]i in a concentration-dependent manner (EC50=10μM). Celecoxib-induced [Ca2+]i rise was reduced by 90% by removal of extracellular Ca2+, and by 30% by L-type Ca2+ channel blockers. Celecoxib-induced Mn2+-associated quench of intracellular fura-2 fluorescence also suggests that celecoxib-induced extracellular Ca 2+ influx. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which the increasing effect of celecoxib on [Ca2+]i was greatly inhibited. Conversely, pretreatment with celecoxib to deplete intracellular Ca 2+ stores totally prevented thapsigargin from releasing more Ca 2+. U73122, an inhibitor of phoispholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca2+ mobilizer)-induced, but not celecoxib-induced, [Ca2+]i rise. Pretreatment with phorbol 12-myristate 13-acetate and forskolin to activate protein kinase C and adenylate cyclase, respectively, partly inhibited celecoxib-induced [Ca 2+]i rise in Ca2+-containing medium. Separately, overnight treatment with 1-100μM celecoxib inhibited cell proliferation in a concentration-dependent manner. These findings suggest that in human osteoblasts, celecoxib increases [Ca2+]i by stimulating extracellular Ca2+ influx and also by causing intracellular Ca2+ release from the endoplasmic reticulum via a phospholiase C-independent manner. Celecoxib may be cytotoxic at higher concentrations.

Original languageEnglish
Pages (from-to)1123-1130
Number of pages8
JournalBiochemical Pharmacology
Volume67
Issue number6
DOIs
StatePublished - 15 03 2004
Externally publishedYes

Keywords

  • Ca
  • Ca stores
  • Celecoxib
  • Fura-2
  • MG63
  • Osteoblasts

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