Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis

• Published in: Blood Vol. 94; no. 6; pp. 1987 - 1997
• Main Authors: KUKITA, A, KUKITA, T, OUCHIDA, M, MAEDA, H, YATSUKI, H, KOHASHI, O
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.09.1999
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Humans; Male; Mice; Molecular and cellular biology; Molecular Sequence Data; Osteoblasts - cytology; Osteoclasts - cytology; Osteoclasts - metabolism; Rats; Rats, Sprague-Dawley; Repressor Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Tumor Cells, Cultured; Zinc Fingers; Vertebrata; Mammalia; Rat; Hematopoiesis; Zinc finger structure; Animal; Rodentia; Osteoclast; Cell differentiation; Transcription factor; Molecular domain; Protein
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v94.6.1987

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.