Kukita, A; Kukita, T; Nagata, K; Teramachi, J; Lin, Y J; Yoshida, H; Miyamoto, H; Gay, S; Pessler, F; Shobuike, T (2011). The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-induced osteoclast formation in vitro and in vivo. Arthritis and Rheumatism, 63(9):2744-2754.
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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 (FBI-1 in humans, OCZF in rats, and LRF, formerly also called Pokemon, in mice) in RA and its role in osteoclastogenesis in vivo. METHODS.: The expression of FBI-1 and OCZF in subchondral osteoclasts was investigated using human RA and rat adjuvant arthritis with immunostaining and in situ hybridization, respectively. Transgenic (Tg) mice were generated which overexpress OCZF under the control of the cathepsin K promoter. Bone mineral density and bone histomorphometric analysis in OCZF Tg mice was 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 adjuvant arthritis and human RA. RANKL increased LRF mRNA and nuclear localized LRF protein in both primary and established macrophages. OCZF Tg mice showed significantly decreased bone volume. The number of osteoclasts but not osteoblasts was increased in long bones of OCZF Tg mice. In addition, osteoclast survival was promoted in OCZF Tg mice. Conversely, inhibition of LRF expression suppressed the formation of osteoclasts from macrophages in vitro. CONCLUSION.: These data suggest that 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.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine|
|DDC:||610 Medicine & health|
|Deposited On:||06 Jun 2011 13:19|
|Last Modified:||27 Nov 2013 17:28|
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