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

Biochem Pharmacol. 2004 Mar 15;67(6):1123-30. doi: 10.1016/j.bcp.2003.11.004.


In human osteoblasts, the effect of the widely prescribed cyclooxygenase-2 inhibitor celecoxib on intracellular Ca(2+) concentrations ([Ca(2+)](i)) and cell proliferation was explored by using fura-2 and the tetrazolium assay, respectively. Celecoxib at concentrations greater than 1microM caused a rapid rise in [Ca(2+)](i) in a concentration-dependent manner ( EC 50= 10 microM). Celecoxib-induced [Ca(2+)](i) rise was reduced by 90% by removal of extracellular Ca(2+), and by 30% by l-type Ca(2+) channel blockers. Celecoxib-induced Mn(2+)-associated quench of intracellular fura-2 fluorescence also suggests that celecoxib-induced extracellular Ca(2+) influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of celecoxib on [Ca(2+)](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 Ca(2+) mobilizer)-induced, but not celecoxib-induced, [Ca(2+)](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 Ca(2+)-containing medium. Separately, overnight treatment with 1-100microM celecoxib inhibited cell proliferation in a concentration-dependent manner. These findings suggest that in human osteoblasts, celecoxib increases [Ca(2+)](i) by stimulating extracellular Ca(2+) influx and also by causing intracellular Ca(2+) release from the endoplasmic reticulum via a phospholiase C-independent manner. Celecoxib may be cytotoxic at higher concentrations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Calcium / metabolism*
  • Calcium Signaling / drug effects*
  • Celecoxib
  • Cell Division / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fura-2 / metabolism
  • Humans
  • Osteoblasts / drug effects*
  • Pyrazoles
  • Sulfonamides / pharmacology*
  • Tetrazolium Salts / chemistry
  • Type C Phospholipases / physiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Sulfonamides
  • Tetrazolium Salts
  • Type C Phospholipases
  • Celecoxib
  • Calcium
  • Fura-2