Oxidative stress-induced intervertebral disc remodelling and elevated stiffness drive idiopathic scoliosis in preclinical models

Patrick G. Pumputis, Ran Xu, Josh Gopaul, Arash Panahifar, Vida Erfani, Jenica L. M. Van Gennip, B. Frank Eames, Nikan Fakhari, Jerome Baranger, David E. Lebel, Olivier Villemain () and Brian Ciruna ()
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Patrick G. Pumputis: The Hospital for Sick Children
Ran Xu: The Hospital for Sick Children
Josh Gopaul: The Hospital for Sick Children
Arash Panahifar: Canadian Light Source
Vida Erfani: The Hospital for Sick Children
Jenica L. M. Van Gennip: The Hospital for Sick Children
B. Frank Eames: University of Saskatchewan
Nikan Fakhari: The Hospital for Sick Children
Jerome Baranger: The Hospital for Sick Children
David E. Lebel: The Hospital for Sick Children
Olivier Villemain: The Hospital for Sick Children
Brian Ciruna: The Hospital for Sick Children

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Adolescent idiopathic scoliosis (AIS) is the most prevalent pediatric spine disorder, developing in the absence of obvious physiological defects. Genome sequencing and functional studies have demonstrated association of musculoskeletal collagen variants and cartilaginous extracellular matrix (ECM) defects in a subset of patients. However, the underlying biological causes of AIS remain poorly understood, limiting treatment options. Using multiple zebrafish AIS models, we demonstrate that reduction-oxidation (redox) imbalances induce cell stress and collagen remodelling within intervertebral segments of the developing spine. Mutant spines are consequently stiffer, as measured by shear wave elastography, and exhibit deformations of intervertebral structures. Remarkably, elevated stiffness and intervertebral ECM phenotypes are detectable prior to scoliosis onset, suggesting a causal relationship, and can be suppressed by antioxidant treatment. Together, our preclinical studies implicate oxidative stress-induced intervertebral deformations in the pathogenesis of AIS and identify elevated spine stiffness and redox imbalance as plausible first-in-kind prognostic biomarkers and therapeutic targets.

Date: 2025
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DOI: 10.1038/s41467-025-63742-2

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