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• W4281707196 abstract "Background. The loss of muscle mass in rheumatoid arthritis (RA), termed rheumatoid cachexia, is predicted to result from the complex interactions between different cell types involved in the maintenance of skeletal muscle mass, namely, myoblasts, fibroblasts, and macrophages. The complexity within the muscle is further highlighted by the incidence of nonresponsiveness to current RA treatment strategies. Method. This study aimed at determining differences in the cellular responses in a novel human primary cell triple coculture model exposed to serum collected from nonarthritic controls (NC), RA treatment naïve (RATN), and RA treatment-nonresponding (RATNR) patients. Bone morphogenetic protein-7 (BMP-7) was investigated as a treatment option. Results. Plasma analysis indicated that samples were indeed representative of healthy and RA patients—notably, the RATNR patients additionally exhibited dysregulated IL-6/IL-10 correlations. Coculture exposure to serum from RATNR patients demonstrated increased cellular growth ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M1> <mi>p</mi> <mo><</mo> <mn>0.001</mn> </math> ), while both hepatocyte growth factor ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M2> <mi>p</mi> <mo><</mo> <mn>0.01</mn> </math> ) and follistatin ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M3> <mi>p</mi> <mo><</mo> <mn>0.001</mn> </math> ) were reduced when compared to NC. Furthermore, decreased concentration of markers of extracellular matrix formation, transforming growth factor-β (TGF-β; <math xmlns=http://www.w3.org/1998/Math/MathML id=M4> <mi>p</mi> <mo><</mo> <mn>0.05</mn> </math> ) and fibronectin ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M5> <mi>p</mi> <mo><</mo> <mn>0.001</mn> </math> ), but increased collagen IV ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M6> <mi>p</mi> <mo><</mo> <mn>0.01</mn> </math> ) was observed following RATNR serum exposure. Under healthy conditions, BMP-7 exhibited potentially beneficial results in reducing fibrosis-generating TGF-β ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M7> <mi>p</mi> <mo><</mo> <mn>0.05</mn> </math> ) and fibronectin ( <math xmlns=http://www.w3.org/1998/Math/MathML id=M8> <mi>p</mi> <mo><</mo> <mn>0.05</mn> </math> ). BMP-7 further exhibited protective potential in the RA groups through reversing the aberrant tendencies observed especially in the RATNR serum-exposed group. Conclusion. Exposure of the triple coculture to RATN and RATNR serum resulted in dysregulated myoblast proliferation and growth, and ECM impairment, which was reversed by BMP-7 treatment." @default.
• W4281707196 created "2022-06-13" @default.
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• W4281707196 date "2022-06-02" @default.
• W4281707196 modified "2023-09-27" @default.
• W4281707196 title "Therapeutic Benefit in Rheumatoid Cachexia Illustrated Using a Novel Primary Human Triple Cell Coculture Model" @default.
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• W4281707196 doi "https://doi.org/10.1155/2022/1524913" @default.
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