A novel growth-friendly system alleviates pulmonary dysplasia in early-onset scoliosis combined with thoracic insufficiency syndrome: Radiological, pathological, and transcriptomic assessments

Ying Zhang; Quan Li; Zhiyue Shi; Qitang Li; Xinfei Dai; Cheng Pan; Yujian Ma; Rongshuang Yan; Derui Fei; Jingming Xie

doi:10.1016/j.heliyon.2024.e27887

A novel growth-friendly system alleviates pulmonary dysplasia in early-onset scoliosis combined with thoracic insufficiency syndrome: Radiological, pathological, and transcriptomic assessments

Heliyon. 2024 Mar 13;10(6):e27887. doi: 10.1016/j.heliyon.2024.e27887. eCollection 2024 Mar 30.

Authors

Ying Zhang¹, Quan Li¹, Zhiyue Shi¹, Qitang Li¹, Xinfei Dai¹, Cheng Pan¹, Yujian Ma¹, Rongshuang Yan¹, Derui Fei¹, Jingming Xie¹

Affiliation

¹ Department of Orthopaedics, the Second Affiliated Hospital of Kunming Medical University, China.

Abstract

Background: The posterior procedure utilizing growth-friendly techniques is the golden standard for patients with early-onset scoliosis combined with thoracic insufficiency syndrome (EOS + TIS). Pulmonary hypoplasia is the main cause of dying prematurely in the EOS + TIS. This study assessed the therapeutic impact of a novel growth-friendly system on the pulmonary development of piglet's EOS + TIS model.

Methods: The animal procedure period lasts 12 weeks, of which the construction of the EOS + TIS was performed at 0-8 weeks, and implantation of a novel growth-friendly system was applied at 8-12 weeks. During the animal procedure, X-rays and CT were performed to observe scoliosis, thorax, and lungs. After 12 weeks, pathological changes in lung tissue were assessed using HE and IHC staining. RNA-seq characterized novel growth-friendly system-associated differentially expressed genes (DEGs) and validated using RT-qPCR, western blotting, and IHC.

Results: Implantation of the novel growth-friendly system increased body weight, body length, and total lung volume, as well as decreased the coronal and sagittal Cobb angles for the EOS + TIS model. It also ameliorated EOS + TIS-induced thickening of the alveolar wall, increased alveolar spaces, and decreased alveolar number and diameter. In lung tissue, a total of 790 novel growth-friendly system-associated DEGs were identified, and they were mainly involved in the regulation of immune, inflammatory, calcium transport, and vascular development. Among these DEGs, BDKRB1, THBS1, DUSP1, IDO1, and SPINK5 were hub genes, and their differential expression was consistent with RNA-seq results in lung tissues.

Conclusion: The novel growth-friendly system has mitigated scoliosis and pulmonary hypoplasia in the EOS + TIS model. We further elucidate the molecular mechanisms underlying the amelioration of pulmonary hypoplasia.

Keywords: Early-onset scoliosis; Growing rod; Pathology; Pulmonary hypoplasia; Radiology; Thoracic insufficiency syndrome; Transcriptomics.