2004 Fiscal Year Final Research Report Summary
Mechanism of hyaluronan depolymerization due to Reactive oxygen species (ROS) produced by synoviocytes cultured in hypoxia, resulting synovial proliferation.
| Project/Area Number |
14571411
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Kinki University |
|---|
Principal Investigator |
AKAGI Masao Kinki University, School of Med., Associate Professor, 医学部, 助教授 (00273441)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SOEN S Kinki University, hospital, Professor, 医学部附属病院, 教授 (10142598)
FUKUDA K Kinki University, School of Med., Professor, 医学部附属病院, 教授 (50201744)
NONAKA T Kinki University, School of Med., Lecturer, 医学部, 講師 (70268407)
OH M Kinki University, hospital, Assistant, 医学部附属病院, 助手 (20319734)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | Osteoarthrosis / Synovium / Cartilage / Hyaluronan / Depolymerization / Mechanical stress / Reactive oxygen species |
|---|
| Research Abstract |
Etiology of osteoarthritis is supposed to involve cartilage degeneration and synovial proliferation. We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (NA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action. ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument (FX-3000). Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity, catalysing the dismutation of superoxide anion into hydrogen peroxide, and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively. ROS depolymerized HA molecules. Cyclic tensile strech depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress. These data suggest that ROS play an important role in mechanical stress-induced HA depolymerization. Depolymerized HA may stimulate synovial proliferation and activate synovial inflammation.
|
