C. Garcia et al., EFFECTS OF SYNTHETIC PEPTIDO-LEUKOTRIENES ON BONE-RESORPTION IN-VITRO, Journal of bone and mineral research, 11(4), 1996, pp. 521-529
Peptido-leukotrienes are short-lived organic molecules known to have p
otent biological effects as mediators of inflammation, hypersensitivit
y and respiratory disorders, However, little is known concerning their
effects on bone cells, We have shown previously that stromal cells is
olated from a human giant cell tumor secrete 5-HETE (5-hydroxyeicosate
traenoic acid) and the peptido-leukotrienes, also known as the cystein
yl leukotrienes LTC(4), LTD(4), and LTE(4). These eicosanoids,were sho
wn to stimulate the multinucleated giant cells obtained from these tum
ors to form resorption lacunae on sperm whale dentine, Here, we show t
hat the peptido-leukotrienes also stimulate isolated avian osteoclast-
like cells to form resorption lacunae and to increase their content of
tartrate-resistant acid phosphatase. LTD(4) increased Ca-45 release f
rom murine calvarial bone organ cultures, but not from fetal rat long
bone cultures, Isolated avian osteoclast-like cells were chosen to per
form receptor binding studies, as this population is the most homogeno
us source of osteoclasts available. After the precursors had fused to
form multinucleated cells, receptor binding assays were performed, Sca
tchard analysis of saturation binding data showed a single class of bi
nding sites, with a dissociation constant (K-d) of 0.53 nM and a recep
tor density of 5,200 receptors per cell, Competition binding studies s
howed receptor specificity using a specific LTD, receptor antagonist Z
M 198,615, These data show that the peptido-leukotrienes activate high
ly enriched populations of isolated avian osteoclast-like cells, and a
lso that specific LTD(4) receptors are present in this cell population
.