Anti-inflammatory effect of hesperidin enhances chondrogenesis of human mesenchymal stem cells for cartilage tissue repair

Shipeng Xiao,Hongwei Gao,Shenghou Liu,Heng Zhao,Ningji Gong,Jianqiang Bi,Mingzhi Gong,Deguo Xing,Wenguang Liu

doi:10.1186/s12950-018-0190-y

Abstract

BackgroundArticular cartilage diseases are considered a major health problem, and tissue engineering using human mesenchymal stem cells (MSCs) have been shown as a promising solution for cartilage tissue repair. Hesperidin is a flavonoid extract from citrus fruits with anti-inflammatory properties. We aimed to investigate the effect of hesperidin on MSCs for cartilage tissue repair. MSCs were treated by hesperidin, and colony formation and proliferation assays were performed to evaluate self-renewal ability of MSCs. Alcian blue staining and Sox9 expression were measured to evaluate chondrogenesis of MSCs. Secretion of pro-inflammatory cytokines IFN-γ, IL-2, IL-4 and IL-10, and expression of nuclear factor kappa B (NF-κB) subunit p65 were also assessed.ResultsHesperidin improved self-renewal ability and chondrogenesis of MSCs, inhibited secretion of pro-inflammatory cytokines IFN-γ, IL-2, IL-4 and IL-10, and suppressed the expression of p65. Overexpression of p65 was able to reverse the hesperidin inhibited secretions of pro-inflammatory cytokines, and abolish the enhancing effect of hesperidin on chondrogenesis of MSCs.ConclusionHesperidin could serve as a therapeutic agent to effectively enhance chondrogenesis of human MSCs by inhibiting inflammation to facilitate cartilage tissue repair.

Highlights

Articular cartilage diseases are considered a major health problem, and tissue engineering using human mesenchymal stem cells (MSCs) have been shown as a promising solution for cartilage tissue repair
MSCs cells were challenged with different doses of hesperidin (0, 1, 5 and 10 μM), and the self-renewal capacity was assessed by colony formation and proliferation assays
5 μM of hesperidin was chosen as the optimal dosage for the subsequent experiments in the current study, and to our best knowledge, these findings provided the first evidence that hesperidin improved self-renewal ability of patient-derived MSCs

Summary

Introduction

Articular cartilage diseases are considered a major health problem, and tissue engineering using human mesenchymal stem cells (MSCs) have been shown as a promising solution for cartilage tissue repair. The cartilage provides a low friction on the articular surfaces of the bone, and serves as an impact absorber for joint movement by covering the load-bearing surface [3, 4] It possesses a low capacity for repair and regeneration due to the absence of vascular, lymphatic and neural networks as well as the lack of sufficient progenitor cells within the cartilage [5, 6]. Implantation of a prosthetic device is performed to replace the living cartilage tissue, which can marginally rescue joint functions but for merely 10–15 years This procedure poses additional risks of post-surgery complications, including infection and inflammation [18]. An efficient treatment to successfully repair or regenerate articular cartilage tissues is urgently needed

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