Kim Kabsun, Lee Junwon, Kim Jung Ha, Jin Hye Mi, Zhou Bin, Lee Soo Young, Kim Nacksung
Research Institute of Medical Sciences and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Gwangju, Korea.
J Immunol. 2007 May 1;178(9):5588-94. doi: 10.4049/jimmunol.178.9.5588.
Protein inhibitor of activated STAT3 (PIAS3) has been shown to regulate the activity of various transcription factors. In this study, we show that the overexpression of PIAS3 in bone marrow-derived monocyte/macrophage lineage cells attenuates osteoclast formation and down-regulates the expression of NFATc1 and osteoclast-associated receptor (OSCAR), which are important modulators in osteoclastogenesis. PIAS3 has been shown to associate with histone deacetylase 1 as well as with transcription factors, including the microphthalmia transcription factor, NFATc1, and c-Fos. Moreover, overexpression of PIAS3 inhibits the transactivation of target genes such as NFATc1 and OSCAR. This inhibitory effect of PIAS3 is possibly mediated by histone deacetylase 1 recruitment to the promoter regions of NFATc1 and OSCAR. Furthermore, silencing of PIAS3 by RNA interference in osteoclast precursors enhances osteoclast formation as well as gene expression of NFATc1 and OSCAR. Taken together, our results reveal that PIAS3 acts as a modulator in osteoclastogenesis.
活化STAT3蛋白抑制剂（PIAS3）已被证明可调节多种转录因子的活性。在本研究中，我们发现PIAS3在骨髓来源的单核细胞/巨噬细胞系细胞中的过表达会减弱破骨细胞的形成，并下调NFATc1和破骨细胞相关受体（OSCAR）的表达，而这两者是破骨细胞生成过程中的重要调节因子。PIAS3已被证明可与组蛋白去乙酰化酶1以及转录因子相互作用，这些转录因子包括小眼畸形转录因子、NFATc1和c-Fos。此外，PIAS3的过表达会抑制NFATc1和OSCAR等靶基因的反式激活。PIAS3的这种抑制作用可能是通过组蛋白去乙酰化酶1募集到NFATc1和OSCAR的启动子区域来介导的。此外，通过RNA干扰使破骨细胞前体中的PIAS3沉默会增强破骨细胞的形成以及NFATc1和OSCAR的基因表达。综上所述，我们的结果表明PIAS3在破骨细胞生成过程中起调节作用。
