title: The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-induced osteoclast formation in vitro and in vivo.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Microbiology, Faculty of Medicine, Saga University, Saga, Japan. kukita@cc.saga-u.ac.jp
authors: Akiko
authors: A
authors: Kukita
authors: Toshio
authors: T
authors: Kukita
authors: Kengo
authors: K
authors: Nagata
authors: Junpei
authors: J
authors: Teramachi
authors: Yin-Ji
authors: YJ
authors: Li
authors: Hiroki
authors: H
authors: Yoshida
authors: Hiroshi
authors: H
authors: Miyamoto
authors: Steffen
authors: S
authors: Gay
authors: Frank
authors: F
authors: Pessler
authors: Takeo
authors: T
authors: Shobuike