Expression analysis of three isoforms of hyaluronan synthase and hyaluronidase in the synovium of knees in osteoarthritis and rheumatoid arthritis by quantitative real-time reverse transcriptase polymerase chain reaction

Mamoru Yoshida,Takaaki Tanaka,Naoki Itano,Keishi Marumo,Koji Kimata,Shigaku Sai,Katsuyuki Fujii

doi:10.1186/ar1223

Abstract

Hyaluronan is a major molecule in joint fluid and plays a crucial role in joint motion and the maintenance of joint homeostasis. The concentration and average molecular weight of hyaluronan in the joint fluids are reduced in osteoarthritis and rheumatoid arthritis. To elucidate the underlying mechanism, we analyzed the message expression of three isoforms of hyaluronan synthase and hyaluronidase from knee synovium, using real-time reverse transcriptase polymerase chain reaction. Synovia were obtained from 17 patients with osteoarthritis, 14 patients with rheumatoid arthritis, and 20 healthy control donors. The message expression of hyaluronan synthase-1 and -2 in the synovium of both types of arthritis was significantly less than in the control synovium, whereas that of hyaluronidase-2 in the synovium of both arthritides was significantly greater than in the control synovium. The decreased expression of the messages for hyaluronan synthase-1 and -2 and/or the increased expression of the message for hyaluronidase-2 may be reflected in the reduced concentration and decreased average molecular weight of hyaluronan in the joint fluids of patients with osteoarthritis and rheumatoid arthritis.

Highlights

High-molecular-weight (HMW) hyaluronan is a major component of synovial joint fluids [1,2,3,4,5]
HMW hyaluronan has a variety of biologic effects on cells in vitro, such as: the inhibition of prostaglandin E2 synthesis and the release of arachidonic acid induced by interleukin-1 from cultured fibroblasts [7,8]; protection against proteoglycan depletion and cytotoxicity induced by oxygenderived free radicals, interleukin-1, and mononuclear-cellconditioned medium [9,10]; and the suppression of phagocytosis, of locomotion, and of enzyme release by leukocytes and macrophages [11,12,13,14]
We investigated message expression levels for three isoforms of hyaluronan synthases (HASs) and hyaluronidase in knee synovium obtained from control donors and patients with OA or rheumatoid arthritis (RA), by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), in order to confirm whether message levels differed

Summary

Introduction

High-molecular-weight (HMW) hyaluronan (average molecular weight 6–7 × 106 Da) is a major component of synovial joint fluids [1,2,3,4,5]. It physically acts as a viscous lubricant for slow joint movements, such as walking, and as an elastic shock absorber during rapid movements, such as running [6]. Reductions in the concentration and average molecular weight of hyaluronan in knee synovial fluids from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) have been reported [2,3,20,21,22,23,24,25]. These reductions indicate hyaluronan's involvement in the pathogenesis of these joint disorders and are reflected in the pathological changes of hyaluronan metabolism

Methods

Results

Conclusion