The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-induced osteoclast formation in vitro and in vivo

Akiko Kukita, Toshio Kukita, Kengo Nagata, Junpei Teramachi, Yin Ji Li, Hiroki Yoshida, Hiroshi Miyamoto, Steffen Gay, Frank Pessler, Takeo Shobuike

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Objective Since transcription factors expressed in osteoclasts are possible targets for regulation of bone destruction in bone disorders, we investigated the expression of the transcription factor FBI-1/OCZF/LRF (in humans, factor that binds to inducer of short transcripts of human immunodeficiency virus type 1; in rats, osteoclast-derived zinc finger; in mice, leukemia/lymphoma-related factor) in patients with rheumatoid arthritis (RA), and assessed its role in osteoclastogenesis in vivo. Methods Expression of FBI-1/OCZF was investigated in subchondral osteoclasts in human RA and in rat adjuvant-induced arthritis (AIA) using immunostaining and in situ hybridization, respectively. Transgenic mice overexpressing OCZF (OCZF-Tg) under the control of the cathepsin K promoter were generated, and bone mineral density and bone histomorphometric features were determined by peripheral quantitative computed tomography, calcein double-labeling, and specific staining for osteoclasts and osteoblasts. LRF/OCZF expression and the consequence of LRF inhibition were assessed in vitro with RANKL-induced osteoclast differentiation. Results FBI-1/OCZF was detected in the nuclei of osteoclasts in rat AIA and human RA. RANKL increased the levels of LRF messenger RNA and nuclear-localized LRF protein in primary macrophages. In OCZF-Tg mice, bone volume was significantly decreased, the number of osteoclasts, but not osteoblasts, was increased in long bones, and osteoclast survival was promoted. Conversely, inhibition of LRF expression suppressed the formation of osteoclasts from macrophages in vitro. Conclusion FBI-1/OCZF/LRF regulates osteoclast formation and apoptosis in vivo, and may become a useful marker and target in treating disorders leading to reduced bone density, including chronic arthritis.

Original languageEnglish
Pages (from-to)2744-2754
Number of pages11
JournalArthritis and Rheumatism
Issue number9
Publication statusPublished - Sept 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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