Abstract

Purpose:To elucidate if the differences found in the physico-chemical and rheological behaviour of Hyaluronic Acids result in different in vivo activity. For this purpose two Hyaluronic Acids (HA), HA-1 and HA-2, with similar molecular weight but different percentage of concentration variation, were compared through an osteoarthritis model.Methods and Materials:Osteoarthritis was induced in white New Zealand rabbits by anterior cruciate ligament section. After the induction period, the animals were allocated to receive HA-1 or HA-2 intra-articularly in one knee whereas the contralateral knee was used as Operated Control. An additional group of non-operated animals was used as Healthy Controls. Samples of cartilage were taken for different measures: apoptosis, nitric oxide (nitrites) and hyaluronic acid in synovial fluid.Results:The administration of HA-1 had a significant inhibitor effect on apoptosis of the chondrocytes compared to operated untreated animals (p = 0.0089), whereas this difference was not observed in the HA-2 knees. Levels of nitrites determined by HPLC in the HA-1 knees were similar to those in the Healthy group (p = 0.6551) whereas they were significantly higher in Operated Control and HA-2 groups (p = 0.0001). The comparison between HA-1 and HA-2 also revealed significantly lower levels of nitrites in the HA-1 knees (p = 0.0001). Values of hyaluronic acid in synovial fluid did not show statistical differences between the different study groups.Conclusions:HA-1 and HA-2 showed different physico-chemical characteristics and these differences have resulted in different in vivo behaviour. As a consequence, not all the HA with similar molecular weight can be considered as equivalent.

Highlights

  • The administration of Hyaluronic Acid (HA)-1 had a significant inhibitor effect on apoptosis of the chondrocytes compared to operated untreated animals (p = 0.0089), whereas this difference was not observed in the HA-2 knees

  • Levels of nitrites determined by High Performance Liquid Chromatography (HPLC) in the HA-1 knees were similar to those in the Healthy group (p = 0.6551) whereas they were significantly higher in Operated Control and HA-2 groups (p = 0.0001)

  • Hyaluronic Acid (HA) is responsible for the viscoelastic properties of synovial fluid, which is greatly diminished in osteoarthritic joints in both concentration and molecular weight [1]

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Summary

Introduction

Hyaluronic Acid (HA) is responsible for the viscoelastic properties of synovial fluid, which is greatly diminished in osteoarthritic joints in both concentration and molecular weight [1]. The main objective of intra-articular treatment with HA is to restore the viscoelastic properties of the synovial fluid. In vitro studies [4, 5] have demonstrated the protective effects of HA on the cartilage in experimental models of osteoarthritis. Other in vitro studies have demonstrated that HA has beneficial effects on the extra-cellular matrix [6], the immune system cells [7] and inflammation mediators [8]. There are several preparations of HA authorized for the treatment of osteoarthritis from different sources, manufacturing process, molecular weight and final concentration. A recent study [9] made it clear that

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