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Hepatocyte growth factor is involved in formation of osteoclast‐like cells mediated by clonal stromal cells (MC3T3‐G2/PA6)
Author(s) -
Sato Takuya,
Hakeda Yoshiyuki,
Yamaguchi Yuji,
Mano Hiroshi,
Tezuka KenIchi,
Matsumoto Kunio,
Nakamura Toshikazu,
Mori Yoshihisa,
Yoshizawa Kenji,
Sumitani Koji,
Kodama Hiroaki,
Kumegawa Masayoshi
Publication year - 1995
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.1041640124
Subject(s) - hepatocyte growth factor , stromal cell , osteoclast , multinucleate , paracrine signalling , microbiology and biotechnology , chemistry , haematopoiesis , growth factor , cell fusion , cell , biology , stem cell , cancer research , biochemistry , in vitro , receptor
Osteoclast formation from hemopoietic precursors has been shown to require the support of stromal cells in bone tissue. In this study, we demonstrated that hepatocyte growth factor (HGF) is one of the stromal cell‐derived molecules responsible for osteoclast‐like cell formation. For our experimens, we used a coculture system for osteoclastic cell formation and activation in which hemopoietic blast cells are cocultured with calvaria‐derived stromal MC3T3‐G2/PA6 (PA6) cells on dentine slices in the presence of 1, 25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. Addition of anti‐HGF neutralizing IgG to the cocultures inhibited the formation of osteoclastic cells and their dentine‐recorbing activity. We detected a single 6.0‐kb transcript for HGF in PA6 cells, and also recognized immunoreactive Mr. 81,000 and 88,000 forms of HGF in conditioned medium (CM) from PA6 cell cultures, the level of which reached 6 ng/ml. Both the CM and HGF stimulated the proliferation of blast cells synergistically with granulocyte‐macrophage colony‐stimulating factor, resulting in an increased number of osteoclast precursors that respond to 1,25(OH) 2 D 3 that are tartrate‐resistant acid phosphatase‐positive multinucleate cells in stromal cell‐free blast cell cultures in plastic wells. The effect of the CM was diminished by the addition of anti‐HGF IgG. However, neither the CM nor HGF stimulated the formation of osteoclastic cells and pits on dentine slices in the absence of PA6 cells. These results suggest that although HGF cannot completely replace stromal cells, it is one of the paracrine mediators produced by stromal cells that act on proliferation of osteoclastic cell precursors. © 1995 Wiley‐Liss, Inc.