Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression

Yoshiro Yonezawa; Long Guo; Hisaya Kakinuma; Nao Otomo; Soichiro Yoshino; Kazuki Takeda; Masahiro Nakajima; Toshiyuki Shiraki; Yoji Ogura; Yohei Takahashi; Yoshinao Koike; Shohei Minami; Koki Uno; Noriaki Kawakami; Manabu Ito; Ikuho Yonezawa; Kei Watanabe; Takashi Kaito; Haruhisa Yanagida; Hiroshi Taneichi; Katsumi Harimaya; Yuki Taniguchi; Hideki Shigematsu; Takahiro Iida; Satoru Demura; Ryo Sugawara; Nobuyuki Fujita; Mitsuru Yagi; Eijiro Okada; Naobumi Hosogane; Katsuki Kono; Kazuhiro Chiba; Toshiaki Kotani; Tsuyoshi Sakuma; Tsutomu Akazawa; Teppei Suzuki; Kotaro Nishida; Kenichiro Kakutani; Taichi Tsuji; Hideki Sudo; Akira Iwata; Tatsuya Sato; Satoshi Inami; Masaya Nakamura; Morio Matsumoto; Chikashi Terao; Kota Watanabe; Hitoshi Okamoto; Shiro Ikegawa

doi:10.1002/jbmr.4738

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression

Yoshiro Yonezawa, Long Guo, Hisaya Kakinuma, Nao Otomo, Soichiro Yoshino, Kazuki Takeda, Masahiro Nakajima, Toshiyuki Shiraki, Yoji Ogura, Yohei Takahashi, Yoshinao Koike, Shohei Minami, Koki Uno, Noriaki Kawakami, Manabu Ito, Ikuho Yonezawa, Kei Watanabe, Takashi Kaito, Haruhisa Yanagida, Hiroshi TaneichiKatsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Kazuhiro Chiba, Toshiaki Kotani, Tsuyoshi Sakuma, Tsutomu Akazawa, Teppei Suzuki, Kotaro Nishida, Kenichiro Kakutani, Taichi Tsuji, Hideki Sudo, Akira Iwata, Tatsuya Sato, Satoshi Inami, Masaya Nakamura, Morio Matsumoto, Chikashi Terao, Kota Watanabe, Hitoshi Okamoto, Shiro Ikegawa

整形外科学

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

抄録

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression.

本文言語	英語
ページ（範囲）	144-153
ページ数	10
ジャーナル	Journal of Bone and Mineral Research
巻	38
号	1
DOI	https://doi.org/10.1002/jbmr.4738
出版ステータス	出版済み - 01-2023

All Science Journal Classification (ASJC) codes

内分泌学、糖尿病および代謝内科学
整形外科およびスポーツ医学

文献へのアクセス

10.1002/jbmr.4738

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「Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル

Yonezawa, Y., Guo, L., Kakinuma, H., Otomo, N., Yoshino, S., Takeda, K., Nakajima, M., Shiraki, T., Ogura, Y., Takahashi, Y., Koike, Y., Minami, S., Uno, K., Kawakami, N., Ito, M., Yonezawa, I., Watanabe, K., Kaito, T., Yanagida, H., ... Ikegawa, S. (2023). Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression. Journal of Bone and Mineral Research, 38(1), 144-153. https://doi.org/10.1002/jbmr.4738

@article{a5203177e79849b39af42a9d5a15c99a,

title = "Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression",

abstract = "Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression.",

author = "Yoshiro Yonezawa and Long Guo and Hisaya Kakinuma and Nao Otomo and Soichiro Yoshino and Kazuki Takeda and Masahiro Nakajima and Toshiyuki Shiraki and Yoji Ogura and Yohei Takahashi and Yoshinao Koike and Shohei Minami and Koki Uno and Noriaki Kawakami and Manabu Ito and Ikuho Yonezawa and Kei Watanabe and Takashi Kaito and Haruhisa Yanagida and Hiroshi Taneichi and Katsumi Harimaya and Yuki Taniguchi and Hideki Shigematsu and Takahiro Iida and Satoru Demura and Ryo Sugawara and Nobuyuki Fujita and Mitsuru Yagi and Eijiro Okada and Naobumi Hosogane and Katsuki Kono and Kazuhiro Chiba and Toshiaki Kotani and Tsuyoshi Sakuma and Tsutomu Akazawa and Teppei Suzuki and Kotaro Nishida and Kenichiro Kakutani and Taichi Tsuji and Hideki Sudo and Akira Iwata and Tatsuya Sato and Satoshi Inami and Masaya Nakamura and Morio Matsumoto and Chikashi Terao and Kota Watanabe and Hitoshi Okamoto and Shiro Ikegawa",

note = "Funding Information: We thank all participating subjects and clinical staff at collaborating institutes. We also thank Y. Takahashi, T. Isono, T. Kusadokoro, and S. Itoh for their technical assistance. This work was supported by the JSPS KAKENHI Grant (no. 19H03787 to M.M., no. 18H02931 to I.K.) and Grant of Keio Orthopaedic Hosoya Foundation (no.007 to Y.Y.). Publisher Copyright: {\textcopyright} 2022 American Society for Bone and Mineral Research (ASBMR).",

year = "2023",

month = jan,

doi = "10.1002/jbmr.4738",

language = "English",

volume = "38",

pages = "144--153",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Wiley-Blackwell",

number = "1",

}

Yonezawa, Y, Guo, L, Kakinuma, H, Otomo, N, Yoshino, S, Takeda, K, Nakajima, M, Shiraki, T, Ogura, Y, Takahashi, Y, Koike, Y, Minami, S, Uno, K, Kawakami, N, Ito, M, Yonezawa, I, Watanabe, K, Kaito, T, Yanagida, H, Taneichi, H, Harimaya, K, Taniguchi, Y, Shigematsu, H, Iida, T, Demura, S, Sugawara, R, Fujita, N, Yagi, M, Okada, E, Hosogane, N, Kono, K, Chiba, K, Kotani, T, Sakuma, T, Akazawa, T, Suzuki, T, Nishida, K, Kakutani, K, Tsuji, T, Sudo, H, Iwata, A, Sato, T, Inami, S, Nakamura, M, Matsumoto, M, Terao, C, Watanabe, K, Okamoto, H & Ikegawa, S 2023, 'Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression', Journal of Bone and Mineral Research, vol. 38, no. 1, pp. 144-153. https://doi.org/10.1002/jbmr.4738

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression. / Yonezawa, Yoshiro; Guo, Long; Kakinuma, Hisaya その他.
In: Journal of Bone and Mineral Research, Vol. 38, No. 1, 01.2023, p. 144-153.

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

TY - JOUR

T1 - Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression

AU - Yonezawa, Yoshiro

AU - Guo, Long

AU - Kakinuma, Hisaya

AU - Otomo, Nao

AU - Yoshino, Soichiro

AU - Takeda, Kazuki

AU - Nakajima, Masahiro

AU - Shiraki, Toshiyuki

AU - Ogura, Yoji

AU - Takahashi, Yohei

AU - Koike, Yoshinao

AU - Minami, Shohei

AU - Uno, Koki

AU - Kawakami, Noriaki

AU - Ito, Manabu

AU - Yonezawa, Ikuho

AU - Watanabe, Kei

AU - Kaito, Takashi

AU - Yanagida, Haruhisa

AU - Taneichi, Hiroshi

AU - Harimaya, Katsumi

AU - Taniguchi, Yuki

AU - Shigematsu, Hideki

AU - Iida, Takahiro

AU - Demura, Satoru

AU - Sugawara, Ryo

AU - Fujita, Nobuyuki

AU - Yagi, Mitsuru

AU - Okada, Eijiro

AU - Hosogane, Naobumi

AU - Kono, Katsuki

AU - Chiba, Kazuhiro

AU - Kotani, Toshiaki

AU - Sakuma, Tsuyoshi

AU - Akazawa, Tsutomu

AU - Suzuki, Teppei

AU - Nishida, Kotaro

AU - Kakutani, Kenichiro

AU - Tsuji, Taichi

AU - Sudo, Hideki

AU - Iwata, Akira

AU - Sato, Tatsuya

AU - Inami, Satoshi

AU - Nakamura, Masaya

AU - Matsumoto, Morio

AU - Terao, Chikashi

AU - Watanabe, Kota

AU - Okamoto, Hitoshi

AU - Ikegawa, Shiro

N1 - Funding Information: We thank all participating subjects and clinical staff at collaborating institutes. We also thank Y. Takahashi, T. Isono, T. Kusadokoro, and S. Itoh for their technical assistance. This work was supported by the JSPS KAKENHI Grant (no. 19H03787 to M.M., no. 18H02931 to I.K.) and Grant of Keio Orthopaedic Hosoya Foundation (no.007 to Y.Y.). Publisher Copyright: © 2022 American Society for Bone and Mineral Research (ASBMR).

PY - 2023/1

Y1 - 2023/1

N2 - Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression.

AB - Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression.

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