Effect of Androgen Receptor on Bone Sialoprotein Gene Transcription

DOI 77 References
  • Takai Hideki
    Departments of Periodontology, Nihon University School of Dentistry at Matsudo.
  • Ogata Yorimasa
    Departments of Periodontology, Nihon University School of Dentistry at Matsudo. Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo.

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  • 骨シアロタンパク質（ＢＳＰ）遺伝子の転写に対するアンドロゲン受容体の効果

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Abstract

Bone sialoprotein (BSP) is a phosphorylated and sulfated noncollagenous protein that has been shown to have the ability to mediate cell attachment through an Arg-Gly-Asp (RGD) sequence and to bind hydroxyapatite through polyglutamic acid sequences. The restricted distribution and temporal changes in the expression of BSP mRNA and the ability of BSP to nucleate hydroxyapatite crystals indicate the potential role of this protein in the initial mineralization of bone. Androgens are steroid hormones that are essential for skeletal development. The androgen receptor (AR) is a transcription factor and a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. In this study, we analyzed the effects of androgens and the AR on the expression of the BSP using osteoblast-like cells (ROS17/2.8 cells). Increase in AR protein levels was observed with androgen receptor (AR) overexpression in ROS17/2.8 cells. The BSP mRNA levels were also increased by AR overexpression. However, the endogenous and overexpressed BSP mRNA levels were not affected by DHT (10-8M, 24 h). While the luciferase activities in all constructs, including a short construct (nts-116 to +60), were increased by AR overexpression, the basal and luciferase activities enhanced by AR overexpression were not affected by DHT(10-8M, 24 h). The effect of AR overexpression was abrogated by 2 bp mutations in either the cAMP response element (CRE) or the activator protein 1/glucocorticoid response element (AP1/GRE). Gel shift analyses showed that AR overexpression increased binding to the CRE and AP1/GRE elements. Notably, the CRE-protein complexes were supershifted by phospho-CREB antibody, and CREB and AR antibodies disrupted the formation of the complexes. The AP1/GRE-protein complexes were supershifted by c-Fos antibody, and c-Jun and AR antibodies disrupted the formation of the complexes. These studies demonstrate that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene. Nihon Shishubyo Gakkai Kaishi (J Jpn Periodontol) 49 : 27-36,2007.

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