A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures.

Sara Cheleschi,Antonella Fioravanti,Ines Gallo,Stefano Giannotti,Martina Di Meglio,Nila Volpi,Sara Tenti,Nicola Giordano

doi:10.3390/ijms19123909

Abstract

Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were significantly modulated by treatment of OA chondrocytes with adipokines. Visfatin and resistin significantly increased NF-κB activation, while the co-treatment with BAY11-7082 did not change MMPs or Col2a1 levels beyond that caused by single treatment. Visfatin and resistin regulate the expression levels of some miRNA involved in OA pathogenesis and exert catabolic functions in chondrocytes via the NF-κB pathway. These data confirm the complex relationship between adipokines and miRNA.

Highlights

Osteoarthritis (OA) represents the most widespread chronic degenerative joint disorder and is a leading cause of chronic disability, impairment, and reduced quality of life in adult and elderly populations [1]
Regulation of Gene Expression of MMP-1, MMP-13 and Col2a1 after nuclear factor (NF)-κB Inhibition In Figure 6 we showed that the incubation of OA chondrocytes with visfatin (5 μg/mL and 10 μg/mLI)naFnigdurrees6iswtiens(h5o0wnegd/thmatLthaendinc1u0b0atniogn/omf LO)Asicghnoinfidcraoncyttleysuwpitrhegvuislfaattiend(5MμMg/Pm-L1 a(pnd
After the incubation of OA chondrocytes with visfatin and resistin, we demonstrated a significant modulation of a pattern of miRNA implicated in OA pathogenesis, and of some factors involved in cartilage metabolism

Summary

Introduction

Osteoarthritis (OA) represents the most widespread chronic degenerative joint disorder and is a leading cause of chronic disability, impairment, and reduced quality of life in adult and elderly populations [1]. Osteoarthritis is generally accepted to be caused by physical and chemical degenerative changes of the joint tissue, resulting in a progressive degeneration of articular cartilage, osteophyte formation, and synovial membrane low-grade inflammation, leading to the loss of function and pain [2,3,4,5]. Growing evidence indicates that white adipose tissue is an active endocrine organ producing multiple factors, known as adipocytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, as well as adipokines: adiponectin, leptin, resistin, chemerin, and visfatin [10]. Adipokines have shown pleiotropic effects modulating the immune response and affecting bone and cartilage metabolisms [10,11]. Serum levels of resistin are increased in patients with OA of the hand [13,14] and in serum and synovial fluid of patients with knee OA [15,16,17]

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