Effects of synthetic peptido-leukotrienes on bone resorption in vitro

C. Garcia, M. Qiao, D. Chen, M. Kirchen, W. Gallwitz, G. R. Mundy, L. F. Bonewald

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Peptido-leukotrienes are short-lived organic molecules known to have potent biological effects as mediators of inflammation, hypersensitivity and respiratory disorders. However, little is known concerning their effects on bone cells. We have shown previously that stromal cells isolated from a human giant cell tumor secrete 5-HETE (5-hydroxyeicosatetraenoic acid) and the peptido-leukotrienes, also known as the cysteinyl leukotrienes LTC4, LTD4, and LTE4. These eicosanoids were shown to stimulate the multinucleated giant cells obtained from these tumors to form resorption lacunae on sperm whale dentine. Here, we show that the peptido-leukotrienes also stimulate isolated avian osteoclast-like cells to form resorption lacunae and to increase their content of tartrate-resistant acid phosphatase. LTD4 increased 45Ca release from murine calvarial bone organ cultures, but not from fetal rat long bone cultures. Isolated avian osteoclast-like cells were chosen to perform receptor binding studies, as this population is the most homogenous source of osteoclasts available. After the precursors had fused to form multinucleated cells, receptor binding assays were performed. Scatchard analysis of saturation binding data showed a single class of binding sites, with a dissociation constant (K(d)) of 0.53 nM and a receptor density of 5,200 receptors per cell. Competition binding studies showed receptor specificity using a specific LTD4 receptor antagonist ZM 198,615. These data show that the peptido-leukotrienes activate highly enriched populations of isolated avian osteoclast-like cells, and also that specific LTD4 receptors are present in this cell population.

Original languageEnglish (US)
Pages (from-to)521-529
Number of pages9
JournalJournal of Bone and Mineral Research
Volume11
Issue number4
DOIs
StatePublished - Apr 1996
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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