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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2011

Open Access 01-04-2011 | Research article

Intraarticular injection of hyaluronan prevents cartilage erosion, periarticular fibrosis and mechanical allodynia and normalizes stance time in murine knee osteoarthritis

Authors: Anna Plaas, Jun Li, Julie Riesco, Rosalina Das, John D Sandy, Andrew Harrison

Published in: Arthritis Research & Therapy | Issue 2/2011

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Abstract

Introduction

Intraarticular hyaluronan (HA) is used clinically for symptomatic relief in patients with knee osteoarthritis (OA); however, the mechanism of action is unclear. In this study, we examined the effects of a single injection of HA on joint tissue pathology, mechanical allodynia and gait changes (measured by stride times) in a murine model of OA.

Methods

OA was induced in the right knee joint (stifle) of 12-week-old male C57BL/6 mice by transforming growth factor β1 (TGFβ1) injection and treadmill running for 14 days. Gait parameters were quantified by using TreadScan, mechanical allodynia was evaluated with von Frey filaments, and joint pathology was evaluated by scoring of macroscopic images for both cartilage erosion and periarticular fibrosis. HA or saline control was injected 1 day after TGFβ1 injection but before the start of treadmill running.

Results

OA development in this model was accompanied by significant (P < 0.01) enhancement of the stance and propulsion times of affected legs. HA injection (but not saline injection) blocked all gait changes and also protected joints from femoral cartilage erosion as well as tibial and femoral tissue fibrosis. Both HA injection and saline injection attenuated acute allodynia, but the HA effect was more pronounced and prolonged than the saline injection.

Conclusions

We conclude that videographic gait analysis is an objective, sensitive and reproducible means of monitoring joint pathology in experimental murine OA, since stance time appears to correlate directly with OA severity. A single injection of HA prevents acute and prolonged gait changes and ameliorates the cartilage erosion and periarticular fibrosis normally seen in this model. We speculate that the capacity of HA to prevent cartilage erosion results from its normalization of joint biomechanics and its inhibitory effects on periarticular cells, which are involved in tissue hyperplasia and fibrosis. This effect of exogenous HA appears to mimic the protective effects of ablation of Adamts5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) on experimental murine OA, and we speculate that a common mechanism is involved.
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Metadata
Title
Intraarticular injection of hyaluronan prevents cartilage erosion, periarticular fibrosis and mechanical allodynia and normalizes stance time in murine knee osteoarthritis
Authors
Anna Plaas
Jun Li
Julie Riesco
Rosalina Das
John D Sandy
Andrew Harrison
Publication date
01-04-2011
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2011
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3286

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