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Leukemia inhibitory factor inhibits osteoclastic resorption, growth, mineralization, and alkaline phosphatase activity in fetal mouse metacarpal bones in culture
Author(s) -
Van Beek Ermond,
Van Der WeePals Lianne,
Van De Ruit Marjan,
Nijweide Peter,
Papapoulos Socrates,
Löwik Clemens
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080210
Subject(s) - osteoclast , leukemia inhibitory factor , bone resorption , endocrinology , medicine , resorption , chemistry , bone remodeling , alkaline phosphatase , fetus , biology , biochemistry , enzyme , receptor , pregnancy , interleukin 6 , genetics , cytokine
Leukemia inhibitory factor (LIF) has been reported to affect bone metabolism, but results are variable. We examined the effect of mouse recombinant LIF on osteoclastic resorption in fetal bone explants representing different stages of osteoclast development. In cultures of 17‐day‐old fetal mouse metacarpals in which only osteoclast progenitors and precursors are present, resorption (measured as 45 Ca release) was significantly inhibited to 29.2% and to 96.6% in the presence of LIF 100 and 1000 U/ml, respectively. Histologic examination of the explants treated with 1000 U/ml of LIF confirmed the biochemical findings and showed that osteoclast progenitors and precursors remained in the periosteum and did not invade the mineralized matrix. In metacarpals of older fetuses (18‐ and 19‐day‐old) in which the mineralizied cartilage has been invaded by mature osteoclasts, the inhibition of resorption by LIF (1000 U/ml) was 87.9 and 74.7%, respectively, the latter being significantly less than the inhibition observed in 17‐day‐old metacarpal cultures. The inhibitory effect of LIF was absent during concurrent administration of PTH or 1,25‐(OH) 2 D 3 and could be reversed by PTH. In addition, LIF was found to inhibit growth, mineralization, and alkaline phosphatase activity in metacarpals independently of osteoclastic resorption. These results suggest that LIF affects the development rather than the activity of osteoclasts, probably through an effect on the osteogenic cells. LIF may be an important endogenous regulator of bone metabolism.