Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes.

Antonietta Stellavato,Virginia Tirino,Valentina Vassallo,Giovanni Balato,Alessio D’Addona,Anna Virginia Adriana Pirozzi,Chiara Schiraldi,Carlo Ruosi,Annalisa La Gatta,Mario De Rosa

doi:10.1155/2019/4328219

Abstract

High molecular weight hyaluronan (H-HA) has a pivotal role in the maintenance of normal functions of synovial fluid and structure of the articular joint, but it has been shown that its concentration is reduced in patients affected by degenerative cartilage diseases, such as osteoarthritis (OA). The aim of this study was to investigate the anti-inflammatory effects and properties of hybrid cooperative complexes based on high and low molecular weight hyaluronan (HCC) compared to H-HA on human primary cells derived by pathological joints. In addition, the rheological behavior of HCC was evaluated in order to define their potential as viscosupplement gel in degenerated joints. The experiments were performed using an in vitro model of OA based on human chondrocytes and synoviocytes isolated from degenerated joints of patients hospitalized for surgical replacement. In order to assess the anti-inflammatory effects of HCC, we evaluated NF-kB, COMP-2, IL-6, and IL-8 as specific markers at the transcriptional and/or protein level. Moreover, the proliferative properties of HCC were assessed using time lapse video microscopy. We showed that chondrocytes and synoviocytes clearly presented an altered cytokine profile compatible with a severe ongoing inflammation status. H-HA and, above all, HCC significantly reduced levels of the specific biomarkers evaluated and improved cartilage healing. The rheological profile indicated HCC suitability for intra-articular injection in joint diseases. HCC viscoelastic properties and the protective/anti-inflammatory effect on human chondrocytes and synoviocytes suggest the novel HCC-based gels as a valid support for OA management.

Highlights

Osteoarthritis (OA) is a progressive disease of the synovial joints that causes pain and limitation of function worsening the quality of life
Articular cartilage is a connective tissue composed of chondrocytes, a type of cell surrounded by a viscous extracellular matrix (ECM)
Chondrocytes represent about 2-5% of cartilage tissue, while the ECM is composed of water, proteoglycans and glycosaminoglycans (20% of the total weight), type II collagen fibers accounting for 5% of the total [6]

Summary

Introduction

Osteoarthritis (OA) is a progressive disease of the synovial joints that causes pain and limitation of function worsening the quality of life. Synovial fluid plays an essential role in the lubrication of joints, and it is characterized by two types of cellular populations: type A synoviocytes (macrophage-like) and type B synoviocytes (fibroblast-like) The former derive by bone marrow and are totally differentiated [7, 8] while the latter are of mesenchymal origin and display many characteristics of fibroblasts and produce several proteases during the process of cartilage damage [8,9,10]. COMP is produced by various types of mesenchymal cells, including synoviocytes For this reason, this is considered a key marker of cartilage degeneration, and its presence in synovial fluid may help in the evaluation of pathology progression. The aim of this study was to investigate the anti-inflammatory effect and properties of HCC compared to H-HA in an OA in vitro model based on human cells derived from degenerated knee cartilage and the corresponding synovial fluid.

Objectives

Methods

Results

Discussion

Conclusion