Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL

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Yasuda, Hisataka¹; Shima, Nobuyuki¹; Akagawa, Nobuaki N.¹; Yamaguchi, Kyoji¹; Kinosaki, Masahiko¹; Mochizuki, Shin-Ichi¹; Omoyasu, Akihiro T¹; Yano, Kazuki¹; Goto, Masaaki¹; Murakami, Akihiko¹; Tsuda, Eisuke¹; Morinaga, Tomonori¹; Igashio, Kanji H.¹; Udagawa, Nobuyuki²; Tkahashi, Naoyuki²; Suda, Tatsuo²

Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL

Proc Natl Acad Sci USA. March 31, 1998;95(7):3597-3602

©1998 The National Academy of Sciences

Affiliations

¹Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., 519 Ishibashi-machi, Shimotsuga-gun, Tochigi 329-0512, Japan

²Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Abstract

Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/macrophage lineage. Osteoclast-like cells (OCLs) are formed by coculturing spleen cells with osteoblasts or bone marrow stromal cells in the presence of bone-resorbing factors. The cell-to-cell interaction between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL formation. Recently, we purified and molecularly cloned osteoclastogenesis-inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction. Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells. The protein was found to be a member of the membrane-associated tumor necrosis factor ligand family and induced OCL formation from osteoclast progenitors. A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation induced by the protein. Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors. We conclude that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteoclast progenitors for their differentiation into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system.
Links

DOI: 10.1073/pnas.95.7.3597

PubMed: 9520411

WoS: 000072848500051
History

Received: 1997-12-15

Cited Works (2)

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