International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Dlx3 Plays a Role as a Positive Regulator of Osteoclast Differentiation

  • Cha, Ji-Hun (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Ryoo, Hyun-Mo (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Woo, Kyung-Mi (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kim, Gwan-Shik (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Baek, Jeong-Hwa (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
  • Published : 2007.09.30
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Abstract

Dlx3 is a homeodomain protein and is known to playa role in development and differentiation of many tissues. Deletion of four base pairs in DLX3 (NT3198) is causally related to tricho-dento-osseous (TDO) syndrome (OMIM # 190320), a genetic disorder manifested by taurodontism, hair abnormalities, and increased bone density in the cranium. Although the observed defects of TDO syndrome involves bone, little is known about the role of Dlx3 in bone remodeling process. In this study, we examined the effect of wild type DLX3 (wtDlx3) expression on osteoclast differentiation and compared it with that of 4-BP DEL DLX3 (TDO mtDlx3). To examine whether Dlx3 is expressed during RANKL-induced osteoclast differentiation, RAW264.7 cells were cultured in the presence of receptor activator of nuclear factor-B ligand (RANKL). Dlx3 protein level increased slightly after RANKL treatment for 1 day and peaked when the fusion of prefusion osteoclasts actively progressed. When wtDlx3 and TDO mtDlx3 were overexpressed in RAW264.7 cells, they enhanced RANKL-induced osteoclastogenesis and the expression of osteoclast differentiation marker genes such as calcitonin receptor, vitronectin receptor and cathepsin K. Since osteoclast differentiation is critically regulated by the balance between RANKL and osteoprotegerin (OPG), we examined the effect of Dlx3 overexpression on expression of RANKL and OPG in C2C12 cells in the presence of bone morphogenetic protein 2. Overexpression of wtDlx3 enhanced RANKL mRNA expression while slightly suppressed OPG expression. However, TDO mtDlx3 did not exert significant effects. This result suggests that inability of TDO mtDlx3 to regulate expression of RANKL and OPG may contribute to increased bone density in TDO syndrome patients. Taken together, it is suggested that Dlx3 playa role as a positive regulator of osteoclast differentiation via up-regulation of osteoclast differentiation-associated genes in osteoclasts, as well as via increasing the ratio of RANKL to OPG in osteoblastic cells.

Keywords

References

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