Irisin recovers osteoarthritic chondrocytes: a muscle-cartilage cross-talk boosted by physical activity

Abstract Background Physical exercise favors weight loss and ameliorates both articular pain and function in patients suffering from osteoarthritis (OA). Irisin, a myokine released by skeletal muscles upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. The study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro . The hypothesis of this study was that irisin would improve hOAC metabolism and proliferation. Methods hOAC were isolated from osteochondral tissues of 5 patients undergoing total knee joint replacement. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation (Picogreen assay), glycosaminoglycan content (dimethylmethylene blue), type II/X collagen gene expression (Real-Time polymerase chain reaction) and quantification (Western blot and densitometric analysis), p38/ERK MAPK and Akt involvement (Western blot and densitometric analysis) were evaluated in both groups. Results Irisin increased hOAC proliferation ( p < 0.001) and both type II collagen gene expression ( p < 0.001) and protein levels ( p < 0.01), while decreased type X collagen gene expression ( p < 0.05) and protein levels ( p < 0.001). These effects seemed to be mediated by the inactivation of the p38 MAPK and PI3K-Akt intracellular pathways, as irisin reduced phosphorylated p38 (p-p38), ( p < 0.01) and phosphorylated Akt (p-Akt) ( p < 0.001) protein levels. Conclusion Irisin stimulated cell proliferation and anabolism in hOAC through p38 MAPK and PI3K-Akt inactivation in vitro , demonstrating for the first time the existence of a cross-talk between muscle and cartilage.

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Irisin Recovers Osteoarthritic Chondrocytes In Vitro

Cells ◽

10.3390/cells9061478 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1478 ◽

Cited By ~ 1

Author(s):

Gianluca Vadalà ◽

Giuseppina Di Giacomo ◽

Luca Ambrosio ◽

Francesca Cannata ◽

Claudia Cicione ◽

...

Keyword(s):

Gene Expression ◽

Protein Kinase ◽

Protein Quantification ◽

Saline Control ◽

Collagen Gene ◽

Type Ii ◽

Protein Levels ◽

Collagen Gene Expression ◽

Osteoarthritic Chondrocytes

Physical exercise favors weight loss and ameliorates articular pain and function in patients suffering from osteoarthritis. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. This study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro. Our hypothesis was that irisin would improve hOAC metabolism and proliferation. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation, glycosaminoglycan content, type II/X collagen gene expression and protein quantification as well as p38/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK), protein kinase B (Akt), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) involvement were evaluated. Furthermore, gene expression of interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 were investigated following irisin exposure. Irisin increased hOAC cell content and both type II collagen gene expression and protein levels, while decreased type X collagen gene expression and protein levels. Moreover, irisin decreased IL-1, IL-6, MMP-1, MMP-13 and iNOS gene expression, while increased TIMP-1 and TIMP-3 levels. These effects seemed to be mediated by inhibition of p38, Akt, JNK and NFκB signaling pathways. The present study suggested that irisin may stimulate hOAC proliferation and anabolism inhibiting catabolism through p38, Akt, JNK, and NFκB inactivation in vitro, demonstrating the existence of a cross-talk between muscle and cartilage.

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Down-regulation of chondrocyte aggrecan and type-II Collagen gene expression correlates with increases in static compression magnitude and duration

Journal of Orthopaedic Research® ◽

10.1002/jor.1100170608 ◽

1999 ◽

Vol 17 (6) ◽

pp. 836-842 ◽

Cited By ~ 92

Author(s):

Paula M. Ragan ◽

Alison M. Badger ◽

Michael Cook ◽

Vicki I. Chin ◽

Maxine Gowen ◽

...

Keyword(s):

Gene Expression ◽

Type Ii Collagen ◽

Collagen Gene ◽

Type Ii ◽

Down Regulation ◽

Static Compression ◽

Collagen Gene Expression

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Tissue specificity of type I collagen gene expression is determined at both transcriptional and post-transcriptional levels

Molecular and Cellular Biology ◽

10.1128/mcb.4.9.1843-1852.1984 ◽

1984 ◽

Vol 4 (9) ◽

pp. 1843-1852

Author(s):

R J Focht ◽

S L Adams

Keyword(s):

Gene Expression ◽

Rna Structure ◽

Type I Collagen ◽

Translational Efficiency ◽

Type I ◽

Collagen Gene ◽

Differentiated Cells ◽

Collagen Gene Expression

We analyzed the control of type I collagen synthesis in four kinds of differentiated cells from chicken embryos which synthesize very different amounts of the protein. Tendon, skin, and smooth muscle cells were found to have identical amounts of type I collagen RNAs; however, the RNAs had inherently different translatabilities, which were observed both in vivo and in vitro. Chondrocytes also had substantial amounts of type I collagen RNAs, even though they directed no detectable synthesis of the protein either in vivo or in vitro. Type I collagen RNAs in chondrocytes display altered electrophoretic mobilities, suggesting that in these cells the reduction in translational efficiency may be mediated in part by changes in the RNA structure. These data indicate that control of type I collagen gene expression is a complex process which is exerted at both transcriptional and post-transcriptional levels.

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