CDP/Cut Is an Osteoblastic Coactivator of the Vitamin D Receptor (VDR)

• Published in: Journal of bone and mineral research 2010-05, Vol.25 (5), p.1157-1166
• Main Authors: OCHIAI, Eiji, KITAGAWA, Hirochika, TAKEYAMA, Ken-Ichi, YAMAOKA, Kazuyoshi, KATO, Shigeaki, KAMIMURA, Takashi, TAKADA, Ichiro, FUJIYAMA, Sally, SAWATSUBASHI, Shun, KIM, Mi-Sun, MEZAKI, Yoshihiro, TSUSHIMA, Yu, TAKAGI, Ken-Ichiro, AZUMA, Yoshiaki
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Differentiation - drug effects; Fundamental and applied biological sciences. Psychology; Homeodomain Proteins - physiology; Humans; Nuclear Proteins - physiology; Osteoblasts - metabolism; Osteosarcoma - metabolism; Receptors, Calcitriol - genetics; Receptors, Calcitriol - physiology; Repressor Proteins - physiology; Skeleton and joints; Tumor Cells, Cultured; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.091105

Vitamin D plays an important role in regulating bone and calcium metabolism. The actions of vitamin D are mediated through the nuclear vitamin D receptor (VDR), and gene disruption of the VDR in mice causes skeletal disorders. However, the precise role of the VDR in each stage of osteoblastogenesis is not well understood. To address this issue, we used a biochemical approach to identify an osteoblast-specific coregulator of the VDR. Using a GST-fused VDR ligand-binding domain as bait, proteins associated with liganded VDR were purified from nuclear extracts of HOS osteoblastic cells and compared with those of HeLa cells. Among the interactants identified by mass fingerprinting, CCAAT displacement protein (CDP) was found as a novel ligand-dependent VDR interactant in HOS cells, together with other previously reported DRIP/TRAP complex components. Further biochemical analysis showed that complex formation between the VDR and CDP was distinct from the previously known DRIP/TRAP complex and the p160 family coactivator complexes. Transient expression of CDP potentiated VDR-mediated transcriptional activation in HOS cells. Furthermore, modulation of CDP expression levels in osteoblastic SaM-1 cells affected vitamin D-dependent osteoblast differentiation before the maturation (mineralization) stage. These findings suggest that CDP is a novel differentiation stage-specific coactivator of the VDR in osteoblasts.