LINK between Degeneration and Regeneration of Human Intervertebral Discs
Bibliographic record
Abstract
Back pain affects a large portion of the population across all ages and intervertebral disc (IVD) degeneration is its most implicated common cause. Presently, there are no established treatments to prevent, stop, or even retard disc degeneration, and surgery is often the offered option. Previous studies have shown that Link N can act as a growth factor and stimulate the synthesis of proteoglycans and collagens in bovine IVD in vitro and in intact human IVDs ex vivo, as well as increase disc height in a rabbit model of disc degeneration. However, the sequences in Link N involved in modulating cellular activity are not well understood. To determine if disc cells can proteolytically process Link N, human disc cells in monolayer were exposed to native Link N over a 48-hour period and mass spectrometric analysis revealed that a peptide spanning residues 1 to 8 was generated in the presence of AF cells but not NP cells. Link N 1-8 significantly induced proteoglycan production in the presence of IL-1β in both NP and AF cells, confirming that the biological effect is maintained in the first eight amino acids of the peptide and indicating that the effect is sustained in an inflammatory environment. Thus Link N 1-8 could be a promising candidate for biologically induced disc repair, and the identification of such a stable specific peptide may facilitate the design of compounds to promote disc repair and provide alternatives to surgical intervention for early stage disc degeneration. Acknowledgments The authors thank Ms. Areej Khabut for her assistance with mass spectrometry. This work would not have been possible without funding from the Faculty of Medicine McGill University, AO Spine, North American Spine Society and Canadian Institutes of Health Research. We also thank Transplant Quebec for coordinating the retrieval of human lumbar spines through their organ donation program. Lastly, we thank The Crafoord Foundation and the Inga-Britt & Arne Lundberg Foundation for funding the mass spectrometers used in this study. Disclosure of Interest None declared
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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 | 0.000 | 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".