Link N as a Therapeutic Agent for Early Intervertebral Disc Degenertion
Notice bibliographique
Résumé
Purpose Although the disc has limited endogenous repair activity, induced repair of disc tissue may be possible by the intradiscal injection of growth factors to stimulate the production of disc matrix. We previously demonstrated that Link N (DHLSDNYTLDHDRAIH), a naturally occurring peptide generated by the N-terminal proteolytic fragmentation of link protein during tissue turnover, can act as a growth factor in the disc. It can stimulate matrix production in vitro, in vivo and in intact ex vivo human intervertebral discs (IVDs). We have recently discovered that AF cells have the ability to proteolytically process Link N resulting in a fragment spanning amino acid residues one-eight (US Patent # 61870394) – short Link N (sLink N). Our in vitro data indicates that the biologically active sequence is preserved within this fragment and, thus, sLink N could represent a potential stable growth factor able to stimulate disc repair. Separately, we developed a long-term organ culture model with vertebral bone. The purpose of the present study was to evaluate the effect of sLink N and compare its efficacy to Link N in this novel organ culture model of early disc degeneration. Method Caudal IVDs from the tails of 20–24 months old steers were isolated with adjacent vertebral bone. After seven days of preconditioning in culture, degeneration was induced in IVDs by a single injection of 50 μg trypsin into the NP. Seven days after induced-degeneration, the trypsin-treated discs were injected with either sLink N or Link N (100 μg/disc, n = six discs/group). Four of the trypsin-treated degenerate discs were injected with PBS alone to serve as a control for degeneration while four discs served as non-degeneration controls. At two, four and eight weeks post treatment, two discs from each treatment and control groups were processed for biochemical analyses. Proteoglycan (predominantly aggrecan) synthesis in the NP was monitored as sulfated glycosaminoglycan using dimethylmethylene blue dye-binding assay, and Western blotting was performed to determine the expression of aggrecan and type two collagen in the tissue. Results Without intervention, at all time points, the GAG content in degenerate discs dropped to ~50% of that in non-degenerate controls. In contrast, sLink N, significantly increased the GAG and collagen content of the discs compared with that in degeneration control discs. Conclusion The results revealed that sLink N has the ability to restore tissue content in an early state of disc degeneration. These results have implications in relation to using either sLink N in regenerating a functional NP in the degenerated IVD or in retarding disc degeneration. Separately, we have developed and validated a novel long-term IVD organ culture model that retains vertebral bone and easy to prepare. Our model is ideal for testing potential drugs and alternate-based therapies, in addition to investigating the long-term effects of loading paradigms on disc degeneration and repair. Disclosures: None
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».