Inhibition of the effects of rheumatoid synovial fluid cells on chondrogenesis and cartilage breakdown in vitro: possible therapeutical conclusions

1993 ◽  
Vol 64 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Hassan Mohamed-Ali ◽  
Peter Scholz ◽  
Hans-Joachim Merker
Author(s):  
H. Mohamed-Ali ◽  
H. Kolkenbrock ◽  
N. Ulbrich ◽  
H. Sörensen ◽  
K. D. Kramer ◽  
...  

2004 ◽  
Vol 24 (2) ◽  
pp. 71-76 ◽  
Author(s):  
Samuel Solomon ◽  
Madhan Masilamani ◽  
Subhasis Mohanty ◽  
J�rg E. Schwab ◽  
Eva-Maria Boneberg ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Eduardo Branco de Sousa ◽  
Gilson Costa dos Santos Junior ◽  
Ramon Pinheiro Aguiar ◽  
Rafaela da Costa Sartore ◽  
Ana Carolina Leal de Oliveira ◽  
...  

Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its modulatory effect on synovial fluid cells. Synovial fluid was collected from non-OA and OA patients, which was centrifuged to isolate cells. Cells were cultured for 21 days, characterized with specific markers for MSC, and exposed to a specific cocktail to induce chondrogenic, osteogenic, and adipogenic differentiation. Then, we performed a MTT assay exposing SF cells from non-OA and OA patients to a medium containing non-OA and OA synovial fluid. Synovial fluid from non-OA and OA patients was submitted to ELISA to evaluate BMP-2, BMP-4, IL-6, IL-10, TNF-α, and TGF-β1 concentrations and to a metabolomic evaluation using1H-NMR. Synovial fluid cells presented spindle-shaped morphologyin vitro. Samples from OA patients formed a higher number of colonies than the ones from non-OA patients. After 21 days, the colony-forming cells from OA patients differentiated into the three mesenchymal cell lineages, under the appropriated induction protocols. Synovial fluid cells increased its metabolic activity after being exposed to the OA synovial fluid. ELISA assay showed that OA synovial fluid samples presented higher concentration of IL-10 and TGF-β1 than the non-OA, while the NMR showed that OA synovial fluid presents higher concentrations of glucose and glycerol. In conclusion, SFC activity is modulated by OA synovial fluid, which presents higher concentration of IL-10, TGF-β, glycerol, and glucose.


2008 ◽  
Vol 16 ◽  
pp. S200
Author(s):  
M.M. Temple-Wong ◽  
V.W. Wong ◽  
Q.T. Nguyen ◽  
K.M. Keifer ◽  
H.H. Harith ◽  
...  

2008 ◽  
Vol 45 (7) ◽  
pp. 1837-1846 ◽  
Author(s):  
Mary H. Ryan ◽  
Diane Petrone ◽  
Jennifer F. Nemeth ◽  
Evan Barnathan ◽  
Lars Björck ◽  
...  

2012 ◽  
Vol 32 (12) ◽  
pp. 1355-1360 ◽  
Author(s):  
Patrícia M. Brossi ◽  
Raquel Y.A. Baccarin ◽  
Cristina O. Massoco

Blood-derived products are commonly administered to horses and humans to treat many musculoskeletal diseases, due to their potential antioxidant and anti-inflammatory effects. Nevertheless, antioxidant effects have never been shown upon horse synovial fluid cells in vitro. If proved, this could give a new perspective to justify the clinical application of blood-derived products. The aim of the present study was to investigate the antioxidant effects of two blood-derived products - plasma (unconditioned blood product - UBP) and a commercial blood preparation (conditioned blood product - CBP)¹ - upon stimulated equine synovial fluid cells. Healthy tarsocrural joints (60) were tapped to obtain synovial fluid cells; these cells were pooled, processed, stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), and evaluated by flow cytometry for the production of reactive oxygen species (ROS). Upon addition of any blood-derived product here used - UBP and CBP - there was a significant decrease in the oxidative burst of synovial fluid cells (P<0.05). There was no difference between UBP and CBP effects. In conclusion, treatment of stimulated equine synovial cells with either UBP or CBP efficiently restored their redox equilibrium.


2003 ◽  
Vol 48 (7) ◽  
pp. 1873-1880 ◽  
Author(s):  
Michel Neidhart ◽  
Christian A. Seemayer ◽  
Klaus M. Hummel ◽  
Beat A. Michel ◽  
Renate E. Gay ◽  
...  

Author(s):  
H. Kolkenbrock ◽  
H. M. -Ali ◽  
Adelheid Hecker-Kia ◽  
G. Buchlow ◽  
H. Sörensen ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 247.1-247
Author(s):  
A. Damerau ◽  
M. Pfeiffenberger ◽  
A. Lang ◽  
T. Gaber ◽  
F. Buttgereit

Background:Our ultimate goal is to study potential drug candidates in an experimental setting of arthritis. Therefore, we aim to develop a valid humanin vitro3D joint model mimicking features of joint inflammation by applying inflammatory conditions namely immune cells and pro-inflammatory cytokines. Our in vitro3D joint model consists of different components including an osteogenic and chondrogenic part, the joint space filled with synovial fluid, and the synovial membrane. Developed as an alternative experimental setup to animal experiments, our 3D joint model will enable us to study efficiently the effects of potential drug candidates in a human-basedin vitromodel.Objectives:Here, we aimed to demonstrate the suitability of our human-basedin vitro3D osteochondral model by analyzing the influence of the main cytokines involved in the pathogenesis of RA as well as the impact of a specific therapeutic intervention.Methods:Based on human bone marrow-derived mesenchymal stromal cells (hMSCs), we developed 3D bone and cartilage tissue components that were characterized in detail (e.g. cell vitality, morphology, structural integrity) using histological, biochemical and molecular biological methods as well as µCT and scanning electron microscope (SEM). In brief, to establish the osteogenic component, we populated β-tricalcium phosphate (TCP) – mimicking the mineral bony part – with hMSCs, while the scaffold-free cartilage component was generated by cellular self-assembly and intermittent mechanical stimulation (fzmb GmbH). Subsequently, we co-cultivated both tissue components for three weeks to generate an interconnected 3D osteochondral model. To test the suitability, we applied a cocktail of TNFα, IL-6 and MIF using concentrations reported from RA synovial fluid alone or in combination with specific therapeutic drugs and analyzed their impact by qPCR.Results:We verified the osteogenic phenotype of our 3D bone tissue component by demonstrating an increase in mineralized bone volume and the induction of bone-related gene expression (RUNX2,SPP1andCOL1A1) as compared to the corresponding control. Secondly, we verified the chondrogenic phenotype of our cartilage tissue component by HE and Alcian Blue staining as well as by the reduced expression ofCOL1A1and an abundant expression ofCOL2A1. Interestingly, co-cultivation of both components for up to 3 weeks demonstrated colonization, connectivity and initial calcification implying a transitional bridging area. Cytokine stimulation with a cocktail of TNF, IL-6 and MIF leads to an upregulation of the metabolic markerLDHAand the angiogenic markerVEGFin both bone and cartilage. The inflammation markersIL8andTNFare also upregulated in both components, whileIL6is downregulated in bone compared to the unstimulated control. In addition, a cytokine-induced upregulation of matrix-metalloproteases was observed especially in the cartilage component. All these cytokine-related effects could be antagonized with a cocktail of therapeutics (milatuzumab, adalimumab and tocilizumab).Conclusion:The results of our study showed cytokine related effects of both tissue components, which can be therapeutically antagonized. By combining the components in a 96 well format, we aim to provide a mid-throughput system for preclinical drug testing.Acknowledgments:This project is funded by the Federal Ministery of Education and Research (BMBF)Disclosure of Interests:Alexandra Damerau: None declared, Moritz Pfeiffenberger: None declared, Annemarie Lang: None declared, Timo Gaber: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.


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