Suppression of fibrous adhesion by proteoglycan decorin.
Small proteoglycan decorin is known to suppress the bioactivity of TGF-beta through a competitive binding with the cell surface receptors for the cytokine. Based on this knowledge, we hypothesized that decorin could reduce the formation of fibrous adhesion, because our previous study showed the neutralizing antibody to TGF-beta1 has that effect. An intra-articular adhesion model in the rabbit knee joint was employed in this study, and decorin was administered into the joint cavity continuously during the 4 weeks of the experiment. The results of the dose-response study demonstrated that decorin suppresses formation of fibrous adhesion in a dose-dependent manner. When the administration of decorin was limited to shorter periods, this effect was considerably impaired and the necessity of long-term administration was demonstrated. On the other hand, when administered together with TGF-beta1, decorin still suppressed adhesion but to a lesser extent, and it was suggested that this proteoglycan could have other significant mechanism(s) to suppress adhesion besides the neutralization of TGF-beta. Thus, the present study showed that decorin could inhibit adhesion formation by both TGF-beta dependent and independent mechanisms. Considering that decorin exists ubiquitously in the body, its administration might be a promising approach to suppress adhesion.
Fukui
N
N
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Japan. fukuin@msnotes.wustl.edu
Fukuda
A
A
Kojima
K
K
Nakajima
K
K
Oda
H
H
Nakamura
K
K
D000818:Animals; D003094:Collagen / Q000145:classification / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D058575:Decorin; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D016326:Extracellular Matrix Proteins; D007091:Image Processing, Computer-Assisted; D015918:Infusion Pumps, Implantable; D007270:Injections, Intra-Articular; D008297:Male; D011509:Proteoglycans / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013264:Stifle / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D013314:Stress, Mechanical; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D019415:Torque; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1
D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D004247:DNA