Hinoi Eiichi, Iezaki Takashi, Fukasawa Kazuya, Kaneda Katsuyuki
Laboratory of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University.
Venture Business Laboratory, Organization of Frontier Science and Innovation, Kanazawa University.
Yakugaku Zasshi. 2019;139(1):15-18. doi: 10.1248/yakushi.18-00154-1.
Although the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) has been identified as a transcriptional coactivator/repressor in various cells, including bone-resorbing osteoclasts, no attention has been paid to its role in bone-forming osteoblasts. Therefore, in this study we show that Ifrd1 is a critical mediator of both osteoblastogenesis and osteoclastogenesis through its expression in osteoblasts. Ifrd1 deficiency enhanced both osteoblast differentiation and maturation, and increased the expression of Runt-related transcription factor 2 and Osterix. A coculture experiment revealed that Ifrd1 deficient osteoblasts have higher osteoprotegerin (OPG) expression and less ability to support osteoclastogenesis. These findings suggest that Ifrd1 plays a pivotal role in bone homeostasis through its expression in osteoblasts, and represents a therapeutic target for bone disease.
尽管转录调节因子干扰素相关发育调节因子1（Ifrd1）已被确定为包括骨吸收破骨细胞在内的多种细胞中的转录共激活因子/抑制因子，但尚未有人关注其在骨形成成骨细胞中的作用。因此，在本研究中，我们表明Ifrd1通过其在成骨细胞中的表达，是成骨细胞生成和破骨细胞生成的关键介质。Ifrd1缺乏增强了成骨细胞的分化和成熟，并增加了Runt相关转录因子2和Osterix的表达。共培养实验表明，Ifrd1缺陷的成骨细胞具有更高的骨保护素（OPG）表达，且支持破骨细胞生成的能力较低。这些发现表明，Ifrd1通过其在成骨细胞中的表达在骨稳态中起关键作用，并代表了骨疾病的治疗靶点。
