Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factor, mediates osteoclast differentiation induced by RANKL.
Osteoclasts are multinucleated cells that resorb bones, and are derived from hematopoietic cells of the monocyte/macrophage lineage. The receptor activator of NF-kappaB ligand (RANKL, also called ODF/TRANCE/OPGL) stimulates both osteoclast differentiation from osteoclast progenitors and activation of mature osteoclasts. To identify genes responsible for osteoclast differentiation, we used a molecular indexing technique. Here, we report a clone of one of these genes whose transcription is induced by soluble RANKL (sRANKL) in both the RAW264.7 cells of the mouse macrophage cell line and the mouse primary bone marrow cells. The predicted protein was found to be a mouse homologue of Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. Transient transfection experiments revealed that overexpression of JDP2 leads to activation of both tartrate-resistant acid phosphatase (TRAP) and cathepsin K gene promoters in RAW264.7 cells. Infection of mouse primary bone marrow cells with retroviruses expressing JDP2-facilitated sRANKL-mediated formation of TRAP-positive multinuclear osteoclasts. Importantly, antisense oligonucleotide to JDP2 strongly suppressed sRANKL-induced osteoclast formation of RAW264.7 cells. Our findings suggest that JDP2 may play an important role in the RANK-mediated signal transduction system, especially in osteoclast differentiation.
Kawaida
Reimi
R
Biomedical Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan.
Ohtsuka
Toshiaki
T
Okutsu
Junichi
J
Takahashi
Tohru
T
Kadono
Yuho
Y
Oda
Hiromi
H
Hikita
Atsuhiko
A
Nakamura
Kozo
K
Tanaka
Sakae
S
Furukawa
Hidehiko
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012097:Repressor Proteins / Q000378:metabolism*
D002352:Carrier Proteins; C491386:Jundp2 protein, mouse; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012097:Repressor Proteins; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse