DISTINCT ROLES OF HYALURONAN SYNTHASE ISOFORMS IN HUMAN SYNOVIUM

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Three hyaluronan synthase (HAS) isoforms encoded by three distinct genes have been cloned and enzymatically characterized in vitro. Their different biological roles, however, have still been unknown. For the first step of clearing the differences, we investigated the expression profiles of the messenger RNAs for HAS isoforms in human synovium of both normal states and pathological states, which involved osteoarthritis (OA) or rheumatoid arthritis (RA) in knee joints and an adhesive formation of subacromial bursae (SAB) in shoulder joints. Human synovium were obtained at surgery followed by isolation of total RNA. Then, the expression of the messages for HAS isoforms were quantified by real-time RT-PCR relatively between OA, RA or adhesive SAB and the control of normal state. The expression of all three HAS isoforms were detected in the control synovium of both knee joints and SAB in shoulder joints. The expression of the messages for HAS1 in the synovium of OA knee joints was approximately 20% higher than those in control. The expression of the messages for HAS2 and HAS3 in OA was approximately 55% and 10% lower than those in control, respectively. The expression of HAS1 and HAS2 in the pannus synovium of RA knee joints was approximately 70% and 15% lower than those in control, respectively. The expression of HAS3 in RA was approximately a 2.4-fold higher than those in control. In adhesive SAB, The expression of the messages for both HAS1 and HAS2 were not detected in any samples while HAS3 alone expressed in adhesive SAB at approximately a 3-fold higher level than those in control. These findings and the reported studies which have shown the different responses of the expression of HAS isoforms in cytokines indicate the distinct biological roles of HAS isoforms. Taken together with the enzymatic properties of them, it is suggested that HAS1 or HAS2 has an anti-inflammatory or anti-adhesive function, and that HAS3 correlates with a formation of pannus or adhesion.
日本結合組織学会の論文

DISTINCT ROLES OF HYALURONAN SYNTHASE ISOFORMS IN HUMAN SYNOVIUM

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