Irisin Recovers Osteoarthritic Chondrocytes In Vitro.

Gianluca Vadalà,Francesca Cannata,Vincenzo Denaro,Giuseppina Di Giacomo,Rocco Papalia,Claudia Cicione,Luca Ambrosio

doi:10.3390/cells9061478

Gianluca Vadalà, Francesca Cannata + Show 5 more

Open Access

https://doi.org/10.3390/cells9061478

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Journal: Cells	Publication Date: Jun 17, 2020
Citations: 33	License type: CC BY 4.0

Affiliation: Università Campus Bio-Medico

Abstract

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.

Highlights

Osteoarthritis (OA) is a degenerative joint disorder affecting more than 10% of adults older than 60 years of age
We report for the first time that irisin may directly target human osteoarthritic chondrocytes (hOAC) and promote cell proliferation and anabolism by increasing GAG and type II collagen synthesis along with tissue inhibitor of matrix metalloproteinases (TIMP)-1 and
Irisin is secreted by skeletal muscle in response to physical exercise and may theoretically promote chondrocyte anabolism so that cartilage can better adapt to increased load and friction during prolonged exercise

Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disorder affecting more than 10% of adults older than 60 years of age. It is characterized by increasing joint pain and stiffness, often leading to disability, with a tremendous negative impact on patients’ overall functionality and quality of life, as well as on healthcare expenditure [1]. It has been estimated that the average cost for treating OA alone in the United States is higher than the combined cost for treating hypertension and diabetes [2]. Major risk factors for OA include genetic predisposition, female gender, joint injury, and obesity [8]. Apart from mechanical overloading, obesity appears to further impact on OA pathogenesis through Predominant features are articular cartilage damage and thinning, which are associated with chondrocyte hypertrophy, tissue inflammation, and extracellular matrix (ECM) degradation [3,4,5,6,7].

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