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A microRNA regulatory mechanism of osteoblast differentiation

机译：成骨细胞分化的microRNA调控机制

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摘要

Growing evidence shows that microRNAs (miRNAs) regulate various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; however, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast differentiation remains elusive. Here, through comprehensive analysis of miRNAs expression during osteoblast differentiation, we show that miR-206, previously viewed as a muscle-specific miRNA, is a key regulator of this process. miR-206 was expressed in osteoblasts, and its expression decreased over the course of osteoblast differentiation. Overexpression of miR-206 in osteoblasts inhibited their differentiation, and conversely, knockdown of miR-206 expression promoted osteoblast differentiation. In silico analysis and molecular experiments revealed connexin 43 (Cx43), a major gap junction protein in osteoblasts, as a target of miR-206, and restoration of Cx43 expression in miR-206-expressing osteoblasts rescued them from the inhibitory effect of miR-206 on osteoblast differentiation. Finally, transgenic mice expressing miR-206 in osteoblasts developed a low bone mass phenotype due to impaired osteoblast differentiation. Our data show that miRNA is a regulator of osteoblast differentiation.
机译：越来越多的证据表明，microRNA（miRNA）调节脊椎动物和无脊椎动物中的各种发育和体内稳态事件。成骨细胞的分化是骨骼正常发育和获得骨量的关键步骤。然而，非编码小RNA，尤其是miRNA在成骨细胞分化中的生理作用仍然难以捉摸。在这里，通过对成骨细胞分化过程中miRNA表达的全面分析，我们发现miR-206（以前被视为肌肉特异性miRNA）是该过程的关键调节因子。 miR-206在成骨细胞中表达，在成骨细胞分化过程中其表达下降。 miR-206在成骨细胞中的过表达抑制了它们的分化，相反，敲低miR-206表达可促进成骨细胞的分化。在计算机分析和分子实验中，发现连接蛋白43（Cx43）是成骨细胞中的主要间隙连接蛋白，是miR-206的靶标，表达miR-206的成骨细胞中Cx43表达的恢复使它们摆脱了miR-206的抑制作用。 206关于成骨细胞的分化。最后，由于成骨细胞分化受损，在成骨细胞中表达miR-206的转基因小鼠表现出低骨量表型。我们的数据表明，miRNA是成骨细胞分化的调节剂。

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  • 作者

    Hiroyuki lnose; Hiroki Ochi; Ayako Kimura; Koji Fujita; Ren Xu; Shingo Sato; Makiko lwasaki; Satoko Sunamura; Yasuhiro Takeuchi; Seiji Fukumoto; Kuniaki Saito; Takashi Nakamura; Haruhiko Siomi; Hiroshi lto; Yoshiyasu Arai; Ken-ichi Shinomiya; Shu Takeda;

  • 作者单位

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Global Center of Excellence Program,Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Global Center of Excellence Program,Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine and;

    Toranomon Hospital Endocrine Center, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan;

    Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;

    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;

    Department of Developmental and Regenerative Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;

    Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine and;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Global Center of Excellence Program,Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;

    Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine and;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    connexin43; miR-206;

    机译：连接蛋白43;miR-206;
  • 入库时间 2022-08-18 00:42:12

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