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ResearchIn-Press PreviewBone BiologyGenetics Open Access | 10.1172/JCI168783

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis

Xiaolu Wang,1 Ming Yue,2 Jason Pui Yin Cheung,1 Prudence Wing Hang Cheung,1 Yanhui Fan,2 Meicheng Wu,2 Xiaojun Wang,1 Sen Zhao,3 Anas M. Khanshour,4 Jonathan J. Rios,5 Zheyi Chen,2 Xiwei Wang,6 Wenwei Tu,6 Danny Chan,2 Qiuju Yuan,7 Dajiang Qin,7 Guixing Qiu,3 Zhihong Wu,3 Jianguo Zhang,3 Shiro Ikegawa,8 Nan Wu,3 Carol A. Wise,5 Yong Hu,1 Keith Dipp Kei Luk,1 You-Qiang Song,2 and Bo Gao9

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Wang, X. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Yue, M. in: JCI | PubMed | Google Scholar |

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Cheung, J. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Cheung, P. in: JCI | PubMed | Google Scholar |

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Fan, Y. in: JCI | PubMed | Google Scholar |

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Wu, M. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Wang, X. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Zhao, S. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Wang, X. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Chan, D. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Wise, C. in: JCI | PubMed | Google Scholar |

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Hu, Y. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Luk, K. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Find articles by Song, Y. in: JCI | PubMed | Google Scholar

1Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong

2School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong

3Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing, China

4Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

5Sarah M and Charles E Seay Center for Musculoskeletal Research, Scottish Rite for Children, Dallas, United States of America

6Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong

7Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong

8Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan

9School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Published November 14, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI168783.
Copyright © 2023, Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 14, 2023 - Version history
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Abstract

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. As such, treatment of AIS is limited to bracing and/or invasive surgery post onset. Pre-onset diagnosis or preventive treatment remains unavailable. Here we performed a genetic analysis of a large multi-center AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multi-generation families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine uptake activity in cells, leading to an increased extracellular glycine level and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature was sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically-used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for “idiopathic” scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.

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  • Version 1 (November 14, 2023): In-Press Preview
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