Optimisation et caractérisation de la culture de chondrocytes en suspension

Revue de la littérature -- Objectifs et organisation générale du document -- Article -- Low calcium levels in serum-free media maintain chondrocyte phenotype in monolayer culture and reduce chodrocyte aggregation in suspension culture -- Article-chondrocyte cultured in stirred suspension with serum-free medium containing pluronic-68 aggregate and proliferate while maintaining their differentiated phenotype -- Article -- the fate of pluronic F-68 in chondrocytes and CHO cells -- Chondrocyte aggregation in suspension culture is GFOGER-GPP and gbs1 integrin dependent -- Discussion générale

Translational strategies in drug development for knee osteoarthritis.

Osteoarthritis (OA) is a common disease worldwide with large unmet medical needs. To bring innovative treatments to OA patients, we at Merck have implemented a comprehensive strategy for drug candidate evaluation. We have a clear framework for decision-making in our preclinical pipeline, to design our clinical proof-of-concept trials for OA patients. We have qualified our strategy to define and refine dose and dosing regimen, for treatments administered either systemically or intra-articularly (IA). We do this through preclinical in vitro and in vivo studies, and by back-translating results from clinical studies in OA patients

La mise en valeur d'Hannibal à Sagonte: le chef punique comme héros épique à l'aube des Punica

Gigout Anne-Laure. La mise en valeur d'Hannibal à Sagonte: le chef punique comme héros épique à l'aube des Punica. In: Vita Latina, N°181, 2009. pp. 68-82

La mise en valeur d'Hannibal à Sagonte: le chef punique comme héros épique à l'aube des Punica

Gigout Anne-Laure. La mise en valeur d'Hannibal à Sagonte: le chef punique comme héros épique à l'aube des Punica. In: Vita Latina, N°181, 2009. pp. 68-82

Increasing the Medium Osmolarity Reduces the Inflammatory Status of Human OA Chondrocytes and Increases Their Responsiveness to GDF-5

The environment surrounding chondrocytes changes drastically in osteoarthritis (OA). For instance, the osmolarity in cartilage (ranging from 350 to 460 mOsm in healthy tissue) decreases during the progression of OA, reaching 270 mOsm. The objective of this study was to evaluate how osmolarity influences human OA chondrocytes. For this purpose, the osmolarity of the culture medium (340 mOsm) was increased to 380, 420 or 460 mOsm and its effect on the phenotype, matrix production, protease expression, cytokine release and growth and differentiation factor-5 (GDF-5) receptor expression in human OA chondrocytes was evaluated in a monolayer. Afterwards, the same parameters, as well as the responsiveness to GDF-5, were evaluated in 3D culture at 340 and 380 mOsm. Our results revealed that increasing the medium osmolarity increased matrix production but also reduced cytokine release, type I collagen and protease expression. It was also demonstrated that at 380 mOsm, the response to GDF-5 in 3D culture was more robust than at 340 mOsm. For the first time, it was established that a decreased osmolarity plays a role in sustaining inflammation and catabolic activities in OA chondrocytes and decreases their responsiveness to GDF-5. This indicates that osmolarity is a critical aspect of OA pathobiology

Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix

Objective: Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this effect is still unknown. In this study, we aimed to investigate the effects of sprifermin at the cellular level. Design: A combination of different chondrocyte culture systems was used and the effects of sprifermin on proliferation, the phenotype and matrix production were evaluated. The involvement of MAPKs in sprifermin signalling was also studied. Results: In monolayer, we observed that sprifermin promoted a round cell morphology and stimulated both cellular proliferation and Sox9 expression while strongly decreasing type I collagen expression. In 3D culture, sprifermin increased the number of matrix-producing chondrocytes, improved the type II:I collagen ratio and enabled human OA chondrocytes to produce a hyaline extracellular matrix (ECM). Furthermore, we found that sprifermin displayed a ‘hit and run’ mode of action, with intermittent exposure required for the compound to fully exert its anabolic effect. Finally, sprifermin appeared to signal through activation of ERK. Conclusions: Our results indicate that intermittent exposure to sprifermin leads to expansion of hyaline cartilage-producing chondrocytes. These in vitro findings are consistent with the increased cartilage volume observed in the knees of OA patients after intra-articular injection with sprifermin in clinical studies

MOESM1 of Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo

Additional file 1. Aggrecan formation in bovine cartilage explants. Bovine cartilage explants were pre-cultured for 1 week, and then cultured for further 5 weeks with weekly administration (48 h duration) of indicated compounds. CS846 (IBEX Pharmaceuticals Inc.) was measured in conditioned media collected at 1, 3 and 5 weeks of compound-culturing. Values were placebo-corrected and all data presented as means ¹ SEM of six replicate explants. One-way ANOVA was used for multiple comparisons to the placebo group at each time point. Significance levels are indicated by asterisks; *P < 0.05, **P < 0.01, ***P < 0.001. All results are from one study (Study 2)