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Effects of stem cell factor on osteoclast‐like cell formation in long‐term human marrow cultures
Author(s) -
Demulder A.,
Suggs S.V.,
Zsebo K.M.,
Scarcez T.,
Roodman G.D.
Publication year - 1992
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.5650071114
Subject(s) - osteoclast , stem cell factor , haematopoiesis , precursor cell , bone marrow , multinucleate , progenitor cell , growth factor , stem cell , microbiology and biotechnology , biology , chemistry , immunology , cell , in vitro , biochemistry , receptor
Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast‐like multinucleated cells (MNC) in long‐term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long‐term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25‐(OH) 2 D 3 for the second and third weeks of culture significantly enhanced MNC formation. [ 3 H]Thymidine incorporation studies showed that SCF increased the proliferation of MNC precursors. These data suggested that SCF was acting on early MNC precursors. We then tested the capacity of SCF to stimulate the formation of colonies of committed precursors for osteoclast‐like MNC. SCF (20 pg/ml to 20 ng/ml) enhanced osteoclast precursor formation in unfractionated bone marrow mononuclear cells but was unable to increase osteoclast precursor formation when a highly purified population of hematopoietic precursors was used as the target cells for SCF. These data suggest that SCF works in concert with other factors produced by nonhematopoietic marrow cells to increase the precursor pool for osteoclasts and that other factors, such as 1,25‐(OH) 2 D 3 , complete the differentiation process to the mature osteoclast.