Variation in Chondroadherin Abundance and Fragmentation in the Human Scoliotic Disc
Bibliographic record
Abstract
In Brief Study Design. Variation in abundance and structure of chondroadherin (CHAD) were studied in the extracellular matrix (ECM) of scoliotic and normal human discs. Objective. To determine whether CHAD abundance and fragmentation vary between different sides of the scoliotic disc and between scoliotic and normal discs. Summary of Background Data. Scoliosis involves curvature of the spine including wedging of the intervertebral discs (IVDs), resulting in altered mechanical loading, which can influence cell metabolism and matrix structure in the IVD. A protein such as CHAD that can influence both cell metabolism and ECM organization could influence disc pathology in scoliosis. Methods. IVDs were obtained from patients with scoliosis and from normal individuals. A proteomic analysis was performed to identify molecules that exhibit side-specific variations in abundance. In addition, changes in the abundance and fragmentation of CHAD and other members of the leucine-rich repeat protein family were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Aggrecan fragmentation was used as an indicator of proteinase action. Results. The relative amount of CHAD was consistently lower on the concave side of the discs in all patients studied. In addition, proteolytic degradation of CHAD occurred in some patients with scoliosis, but not in normal IVDs. The presence of aggrecan fragments provided evidence for both aggrecanase and metalloproteinase activity in the scoliotic discs although no side-specific difference was found. Other members of the leucine-rich repeat family of proteins did not show evidence of the same consistent variation in abundance between the 2 sides and did not show signs of degradation. Conclusion. As CHAD can interact with both the ECM and the cells, it can provide a mechanism for regulating cell metabolism and ECM structure, and so play a role in promoting matrix homeostasis. Thus, changes in CHAD abundance or structure could be associated with the pathologic changes occurring in the scoliotic IVD. In the human scoliotic intervertebral disc,the abundance of chondroadherinis lower on the concave side versus the convex side. In some individuals with scoliosis, fragmentation of chondroadherinwas evident; such fragmentation was not a feature of the normal intervertebral disc. Changes in chondroadherinfragmentation and abundance could alter disc cell metabolism and participate in the changes in disc structure associated with scoliosis.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".