A Novel Growth-friendly System Alleviates Pulmonary Dysplasia in Early-onset Scoliosis Combined with Thoracic Insufficiency Syndrome: Radiological, Pathological, and Transcriptomic Assessments

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Mar 21

PMID 38509966

Authors

Ying Zhang

Quan Li

Zhiyue Shi

Qitang Li

Xinfei Dai

Cheng Pan

Yujian Ma

Rongshuang Yan

Derui Fei

Jingming Xie

Affiliations

Soon will be listed here.

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.

Citing Articles

Validation of the Korean Version of the 24-Item Early-Onset Scoliosis Questionnaire: A Multicenter Study from the Korean Research Society of Spinal Deformity.

Hwang C, Chang S, Park K, Lee D, Cho J, Matsumoto H Clin Orthop Surg. 2025; 17(1):123-129.

PMID: 39912072 PMC: 11791488. DOI: 10.4055/cios24210.

References

Wang Y, Wang D, Zhang G, Ma B, Ma Y, Yang Y . Effects of spinal deformities on lung development in children: a review. J Orthop Surg Res. 2023; 18(1):246. PMC: 10041811. DOI: 10.1186/s13018-023-03665-0. View

Karol L . The Natural History of Early-onset Scoliosis. J Pediatr Orthop. 2019; 39(Issue 6, Supplement 1 Suppl 1):S38-S43. DOI: 10.1097/BPO.0000000000001351. View

Quint D, Salton G . Migration of luque rods through a laminectomy defect causing spinal cord compression. AJNR Am J Neuroradiol. 1993; 14(2):395-8. PMC: 8332953. View

Eberle C . Failure of fixation after segmental spinal instrumentation without arthrodesis in the management of paralytic scoliosis. J Bone Joint Surg Am. 1988; 70(5):696-703. View

Ouellet J . Surgical technique: modern Luqué trolley, a self-growing rod technique. Clin Orthop Relat Res. 2011; 469(5):1356-67. PMC: 3069294. DOI: 10.1007/s11999-011-1783-4. View

Zhang Y, Shi Z, Li W, Dai X, Li Q, Pan C . A porcine model of early-onset scoliosis combined with thoracic insufficiency syndrome: Construction and transcriptome analysis. Gene. 2023; 858:147202. DOI: 10.1016/j.gene.2023.147202. View

McCarthy R, Luhmann S, Lenke L, McCullough F . The Shilla growth guidance technique for early-onset spinal deformities at 2-year follow-up: a preliminary report. J Pediatr Orthop. 2013; 34(1):1-7. DOI: 10.1097/BPO.0b013e31829f92dc. View

Luque E . Segmental spinal instrumentation for correction of scoliosis. Clin Orthop Relat Res. 1982; (163):192-8. View

McCarthy R, McCullough F . Shilla Growth Guidance for Early-Onset Scoliosis: Results After a Minimum of Five Years of Follow-up. J Bone Joint Surg Am. 2015; 97(19):1578-84. DOI: 10.2106/JBJS.N.01083. View

10.

Thebaud B . Angiogenesis in lung development, injury and repair: implications for chronic lung disease of prematurity. Neonatology. 2007; 91(4):291-7. DOI: 10.1159/000101344. View

11.

Sheehan D, Grayhack J . Pulmonary Implications of Pediatric Spinal Deformities. Pediatr Clin North Am. 2020; 68(1):239-259. DOI: 10.1016/j.pcl.2020.09.012. View

12.

Li J, Liu S . LncRNA GAS5 suppresses inflammatory responses and apoptosis of alveolar epithelial cells by targeting miR-429/DUSP1. Exp Mol Pathol. 2019; 113:104357. DOI: 10.1016/j.yexmp.2019.104357. View

13.

Tsukahara K, Mayer O . Thoracic insufficiency syndrome: Approaches to assessment and management. Paediatr Respir Rev. 2022; 44:78-84. PMC: 9448829. DOI: 10.1016/j.prrv.2022.02.003. View

14.

Cheng W, Kao S, Chen C, Yuliani F, Lin L, Lin C . Amphiregulin induces CCN2 and fibronectin expression by TGF-β through EGFR-dependent pathway in lung epithelial cells. Respir Res. 2022; 23(1):381. PMC: 9797108. DOI: 10.1186/s12931-022-02285-2. View

15.

Breen E, Fu Z, Normand H . Calcyclin gene expression is increased by mechanical strain in fibroblasts and lung. Am J Respir Cell Mol Biol. 1999; 21(6):746-52. DOI: 10.1165/ajrcmb.21.6.3312. View

16.

Kennedy Ii D, Mody P, Gout J, Tan W, Seo K, Olivier A . Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia. Front Cell Infect Microbiol. 2022; 12:886901. PMC: 9177954. DOI: 10.3389/fcimb.2022.886901. View

17.

Penaloza H, Olonisakin T, Bain W, Qu Y, van der Geest R, Zupetic J . Thrombospondin-1 Restricts Interleukin-36γ-Mediated Neutrophilic Inflammation during Pseudomonas aeruginosa Pulmonary Infection. mBio. 2021; 12(2). PMC: 8092289. DOI: 10.1128/mBio.03336-20. View

18.

Penke L, Speth J, Wettlaufer S, Draijer C, Peters-Golden M . Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition. Am J Respir Cell Mol Biol. 2021; 66(1):23-37. PMC: 8803353. DOI: 10.1165/rcmb.2021-0112OC. View

19.

Ruiz G, Torres-Lugo N, Marrero-Ortiz P, Guzman H, Olivella G, Ramirez N . Early-onset scoliosis: a narrative review. EFORT Open Rev. 2022; 7(8):599-610. PMC: 9458941. DOI: 10.1530/EOR-22-0040. View

20.

Alvira C . Aberrant Pulmonary Vascular Growth and Remodeling in Bronchopulmonary Dysplasia. Front Med (Lausanne). 2016; 3:21. PMC: 4873491. DOI: 10.3389/fmed.2016.00021. View