Oxidative stress-induced intervertebral disc remodelling and elevated stiffness drive idiopathic scoliosis in preclinical models
Bibliographic record
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. Scoliosis is a common yet poorly understood pediatric disorder. Using zebrafish disease models, Pumputis et al. identify pervasive cell stress responses as causing spine deformity and present possibilities for new therapies and diagnostic tools.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".