ab22304

Effects of glucosamine hydrochloride on the production of prostaglandin E₂, nitric oxide and metalloproteases by chondrocytes and synoviocytes in osteoarthritis

H. Nakamura, A. Shibakawa, M. Tanaka, T. Kato, K. Nishioka

Department of Bioregulation, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

ABSTRACT
Objectives
To determine the response of glucosamine hydrochloride on chondrocytes and synoviocytes in terms of prostaglandin E₂ (PGE₂), nitric oxide (NO) and matrix metalloproteases (MMPs).

Methods
Chondrocytes and synoviocytes were prepared from joint specimens of patients who underwent total knee arthroplasty for osteoarthritis (OA). Chondrocytes from patients with femoral neck fracture were served as a normal control. Culture cells were stimulated by 5 ng/ml of IL-1b and treated with various concentration of glucosamine hydrochloride (from 1 mg/ml to 500 mg/ml). PGE₂, NO, MMP-1, MMP-3, and MMP-13 levels were evaluated in the culture supernatant. Further, the expression of COX-2 mRNA was studied by semi-quantitative PCR.

Results
With IL-1b stimulation, the levels of these mediators increased dramatically, except for NO from synoviocytes. After stimulation, levels of these mediators in OA chondrocytes were higher than synoviocytes and normal chondrocytes, and the level of MMP-3 was higher than those of MMP-1 and MMP-13. Glucosamine hydrochloride at a concentration of 100 mg/ml suppressed PGE₂ production, and partly suppressed NO production. It also suppressed the production of MMPs from normal chondrocytes and synoviocytes but not from OA chondrocytes.

Conclusion
Glucosamine modulates the metabolism of chondrocytes and synoviocytes and its mode of action differs between cells and conditions.

Key words
Glucosamine, osteoarthritis, chondrocytes, synovial cells, MMP, PGE2, NO, COX-2.

Supported in part by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Please address reprint requests and correspondence to: Hiroshi Nakamura, MD, Institute of Medical Science, St. Marianna University, 2-16-1, Sugao, Miyame-ku, Kawasaki, 216-8512, Japan.
E-mail nakamura@marianna-u.ac.jp