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Asymmetric expression of GPR126 in the convex/concave side of the spine is associated with spinal skeletal malformation in adolescent idiopathic scoliosis population

  • Enjie Xu
  • Tao Lin
  • Heng Jiang
  • Zhe Ji
  • Wei Shao
  • Yichen Meng
  • Rui GaoEmail author
  • Xuhui ZhouEmail author
Original Article

Abstract

Purpose

To determine the relationship between the bone formation-related functions of GPR126 and the structural asymmetry of spine in adolescent idiopathic scoliosis (AIS).

Methods

Vertebral body samples were obtained from 51 AIS patients during spinal surgery between October 2014 and November 2017, and the expression pattern of GPR126 in the convex/concave sides of AIS spine was identified by RT-qPCR. Next, we explored the bone formation-related functions of GPR126 by knocking down and overexpressing GPR126 in human mesenchymal stem cells (hMSC) and further performing osteogenic differentiation. We also applied overexpression of N-terminal fragments derived from GPR126 (GPR126-NTFs) and osteogenic differentiation experiments to determine the functional part of GPR126 in skeletal development.

Results

We provided evidence that GPR126 showed a marked convex/concave asymmetric expression in the spine of AIS. Further RNA detection found that exon6-included transcripts of GPR126 (GPR126-exon6in) were significantly higher expressed in the convex side of AIS patients. Knocking down of GPR126 accelerated ossification of hMSCs during osteogenic differentiation, and overexpression of GPR126-exon6in delayed this process. Overexpression of GPR126-NTFs revealed that NTF is a functional fragment and exon6-included NTF (NTF-exon6in) delayed ossification of hMSCs.

Conclusion

Our findings indicated that GPR126-NTFs play a role in skeletal development, and the inclusion/exclusion of exon6 may regulate the bone formation-related functions of GPR126. The convex/concave asymmetric expression of GPR126-exon6in may be an important factor in abnormal bone formation of AIS.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Keywords

Adolescent idiopathic scoliosis GPR126 Bone formation Transcript N-terminal fragment 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

586_2019_6001_MOESM1_ESM.pptx (8.1 mb)
Supplementary material 1 (PPTX 8303 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Orthopedics, Changzheng HospitalSecond Affiliated Hospital of Second Military Medical UniversityShanghaiPeople’s Republic of China

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