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Effects of interleukin 3 and of granulocyte‐macrophage and macrophage colony stimulating factors on osteoclast differentiation from mouse hemopoietic tissue
Author(s) -
Hattersley G.,
Chambers T. J.
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041420125
Subject(s) - osteoclast , bone resorption , macrophage colony stimulating factor , resorption , haematopoiesis , endocrinology , granulocyte macrophage colony stimulating factor , medicine , macrophage , biology , bone marrow , receptor , chemistry , microbiology and biotechnology , immunology , cytokine , in vitro , stem cell , biochemistry
The effects of granulocyte‐macrophage colony stimulating factor (GM‐CSF), macrophage colony stimulating factor (M‐CSF), and interleukin 3 (IL3) on osteoclast formation were tested by incubation of murine hemopoietic cells on plastic coverslips and bone slices with GM‐CSF, M‐CSF, or IL3, with or without 1,25(OH) 2 vitamin D 3 (1,25(OH) 2 D 3 ). Osteoclastic differentiation was detected after incubation by scanning electron microscopical examination of bone slices for evidence of osteoclastic excavations, and by autoradiographic assessment of cells for 1,25(OH) 2 D 3 ‐calcitonin (CT) binding. The differentiation of CT‐receptor‐positive cells preceded bone resorption, but the number that developed correlated with the extent of bone resorption (r = 0.88). M‐CSF and GM‐CSF substantially reduced bone resorption and CT‐receptor‐positive cell formation. The degree of inhibition of bone resorption could not be attributed to effects on the function of mature cells, since M‐CSF inhibits resorption by such cells only by 50%, and GM‐CSF has no effect. GM‐CSF inhibited the development of mature function (bone resorption) to a greater extent than it inhibited CT‐receptor‐positive cell formation. Since CT‐receptor expression antedated resorptive function, this suggests that GM‐CSF resulted in the formation of reduced numbers of relatively immature osteoclasts. This suggests that it may exert a restraining effect on the maturation of cells undergoing osteoclastic differentiation in response to 1,25(OH) 2 D 3 . Conversely, IL3, which also has no effect on mature osteoclasts, by itself induced CT‐receptor expression but not bone resorption; in combination with 1,25(OH) 2 D 3 it induced a threefold increase in bone resorption and CT‐receptor‐positive cells compared with cultures incubated with 1,25(OH) 2 D 3 alone. IL3 did not induce CT‐receptors in peritoneal macrophages, blood mono‐cytes, or J 774 cells. The results suggest that IL3 induces only partial maturation of osteoclasts, which is augmented or completed by additional factors such as 1,25(OH) 2 D 3 .