Suppressive effects of hyaluronan on MMP-1 and RANTES production from chondrocytes.
The purpose of the study was to examine the effects of hyaluronan (HA) on human chondrocytes in terms of production of MMP-1 and RANTES. Chondrocytes were obtained from patients with osteoarthritis (OA) or femoral neck fracture (control). Chondrocytes in monolayer culture were treated with various molecular weights (1.2, 50, 800 and 1,900 kD) of HA and then stimulated with IL-1beta. Production and expression of MMP-1 and RANTES were quantified by ELISA and real-time polymerase chain reaction (PCR). The response was blocked by anti-CD44 antibody. Production of MMP-1 was significantly suppressed by both 800- and 1,900-kD HA, while production of RANTES was suppressed by 1,900-kD HA. Expression of MMP-1 and RANTES mRNA was inhibited by 1,900-kD HA. Suppressive effects of HA on production of MMP-1 were canceled by treatment of anti-CD44 antibody. Higher CD44 expression was found in OA chondrocytes than in those of control. High-molecular-weight HA suppressed MMP-1 and RANTES production, mediated partly by CD44-HA interaction.
Tanaka
Michiaki
M
Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, Sugao, Kawasaki, 216-8512, Japan.
Masuko-Hongo
Kayo
K
Kato
Tomohiro
T
Nishioka
Kusuki
K
Nakamura
Hiroshi
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000906:Antibodies; C497483:CD44 protein, human; D018946:Chemokine CCL5; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D006820:Hyaluronic Acid; D020781:Matrix Metalloproteinase 1