Abnormal collagen type I production in osteoarthritic subchondral bone is associated with a reduced capacity of osteoblasts to mineralize in vitro
Notice bibliographique
Résumé
Osteoarthritis (OA) is characterized by cartilage loss, synovial inflammation, osteophytes, and abnormal subchondral bone remodeling including sclerosis. Bone sclerosis in OA is due to an abundant osteoid collagen matrix. Collagen type 1 synthesis is increased in in vivo OA bone tissue and there is an abnormal ratio of collagen type 1α1 chains (Coll1α1) to Coll1α2 chains in this tissue. The mechanisms responsible for this abnormal osteoid matrix remain unknown. In this study using in vitro subchondral osteoblasts (Ob) from normal and OA individuals, we investigated the mechanisms responsible for abnormal collagen production. We used primary human subchondral Ob from normal and OA individuals. Cells were stimulated or not with 100 ng/ml parathyroid hormone (PTH), 500 nM prostaglandin E 2 (PGE 2 ) or 50 nM 1,25(OH) 2 D 3 . RNA was extracted with TRIzol and used to perform RT-PCR and real-time PCR of Coll1A1 and Coll1A2. Coll1 synthesis was assessed as the release of the carboxy terminal peptide fragment (CICP), which reflects de novo collagen synthesis. Proteins were separated by SDS-PAGE and detected using selective antibodies against Coll1α1, Coll1α2, or membrane-type 1 or membrane-type 2 matrix metalloprotease (MT1-MMP and MT2-MMP). MMP-2 and MMP-9 activities were assessed by zymography. Mineralization was evaluated by the von Kossa staining of cells after 30 days of culture in the presence or not of 10 ng/ml bone morphogenic protein-2 (BMP-2). Data showed that basal Coll1A1 mRNA levels were significantly increased in OA Ob compared with normal using real-time PCR, whereas Coll1A2 levels in OA Ob were similar to normal. This translated into an α1 to α2 collagen type I ratio of 2.5 in normal Ob whereas it increased to 7.2 in OA Ob. PTH and PGE 2 both reduced Coll1A1 and Coll1A2 mRNA levels in normal Ob yet this was reduced for OA Ob. Indeed, PGE 2 reduced Coll1A1 and Coll1A1 mRNA levels about half as in normal, and the effect of PTH was virtually absent in OA Ob. Basal collagen type I synthesis, determined by the release of the C-terminal propeptide and by western blot analysis, was also higher in OA Ob than normal. MMP-2 and MMP-9 were increased in OA Ob compared with normal as determined by zymography. Western blot analysis showed an increase in MT2-MMP but not in MT1-MMP in OA Ob. Finally, the mineralization of OA Ob was significantly reduced compared with normal as determined by Von Kossa staining under both basal conditions and following BMP-2 stimulation. These results suggest that a cellular defect of OA Ob and an abnormal response to PTH and PGE 2 challenge could explain abnormal production and ratio of α1 to α2 chains of mature collagen type 1 in these cells. Coupled to the increase in MMP activities, this could explain the abnormal collagen remodeling observed in OA bone tissue in vivo .
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,004 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».