Effects of a selective cyclooxygenase-2 inhibitor, celecoxib, on bone resorption and osteoclastogenesis in vitro

Kaoru Igarashi, Je Tae Woo, Paula H Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The effects of an important new anti-inflammatory agent, the selective cyclooxygenase-2 inhibitor celecoxib, on bone resorption and osteoclastogenesis elicited by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), the endotoxin lipopolysaccharide (LPS), and the systemic hormones 1α,25-dihydroxyvitamin D3 and parathyroid hormone were examined in vitro. Bone resorption was evaluated by measuring calcium released into the culture medium in a neonatal mouse calvarial bone organ culture. Osteoclastogenesis was evaluated by measuring tartrate-resistant acid phosphatase activity in the cells in cocultures of bone marrow cells and osteoblastic cells and in macrophage-colony-stimulating factor-dependent bone marrow cell cultures. Celecoxib (0.1μM) completely inhibited the calcium release induced by IL-1β, TNF-α, and LPS. The resorptive effect of 1α,25-dihydroxyvitamin D3 was inhibited partially by celecoxib. In contrast, celecoxib did not inhibit the calcium release elicited by parathyroid hormone or prostaglandin E2. Celecoxib (0.1μM) also markedly inhibited osteoclastogenesis induced by these stimulators of bone resorption except for PGE2 in the coculture system, whereas it failed to inhibit osteoclastogenesis in macrophage-colony-stimulating factor-dependent bone marrow cell cultures. These results indicate that, under certain conditions, cyclooxygenase-2-dependent prostaglandin synthesis is critical for the bone resorption induced by IL-1β, TNF-α, and LPS, and for the osteoclastogenesis induced by these pro-inflammatory molecules and calciotropic hormones. The prevention of prostaglandin synthesis by inflammatory cytokines in bone cells could contribute to the efficacy of celecoxib in preventing bone loss in rheumatoid arthritis.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalBiochemical Pharmacology
Volume63
Issue number3
DOIs
StatePublished - Feb 1 2002

Keywords

  • Bone resorption
  • Calvaria
  • Celecoxib
  • Cylooxygenase-2 inhibitor
  • Osteoclastogenesis
  • Prostaglandin

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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