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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 1987-1997
Osteoclast-Derived Zinc Finger (OCZF) Protein With POZ Domain,
a Possible Transcriptional Repressor, Is Involved in Osteoclastogenesis
Akiko Kukita,
Toshio Kukita,
Mamoru Ouchida,
Hidefumi Maeda,
Hitomi Yatsuki, and
Osamu Kohashi
From the Department of Microbiology, Department of Biochemistry, Saga
Medical School, Saga, Japan; and the Second Department of Anatomy,
Department of Conservative Dentistry, Faculty of Dentistry, Kyushu
University, Fukuoka, Japan.
The differentiation of osteoclasts is regulated by transcription
factors expressed in cells of osteoclast lineage. We isolated here a
potential transcription factor from a cDNA library of an enriched
population of preosteoclasts and osteoclasts. The cDNA encodes a
protein with N-terminal POZ domain and C-terminal
Krüppel-like zinc fingers. We designate this protein as
osteoclast-derived zinc finger (OCZF). OCZF was found to be rat
homologue of mouse leukemia/lymphoma-related factor (LRF). Northern
blot and in situ hybridization analysis showed OCZF mRNA at a
high level in osteoclasts and kidney cells. OCZF had a nuclear
targeting sequence and was localized in the nucleus of transfected
cells. In addition, OCZF specifically bound to the guanine-rich
consensus sequences of Egr-1 and c-Krox. Transient transfection
assays indicate that OCZF can repress transcription activity like other
POZ domain proteins. Furthermore, antisense but not sense
phosphorothioate oligodeoxynucleotides (ODNs) for OCZF cDNA
suppressed the formation of osteoclast-like multinucleated cells (MNCs)
in bone marrow culture, whereas the same ODNs did not significantly
affect the formation of macrophage polykaryons and mononuclear
preosteoclast-like cells (POCs). These results suggest that OCZF is a
unique transcription factor that plays an important role in the late
stage of osteoclastogenesis.
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