Expression of transforming growth factor-beta1 and connective tissue growth factor in the capsule in a rat immobilized knee model.
BACKGROUND
Contracture is a very common complication of joint immobilization in daily examination, but its cause is still unknown. A fibrotic change of the capsule is suggested to be one of the main causes of the joint contracture. The goal of this study was to analyze the expression pattern of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF), which are implicated in fibrosis in the capsule of a rat immobilized knee model.


METHODS
We immobilized the unilateral knee joints of 66 rats in 150 degrees of flexion using a plastic plate and metal screws. Sham operated knee joints of 66 rats had holes drilled and screws inserted but none of them were plated. The capsule from the anterior and posterior portion of the knee joints was harvested at 3 days, 1, 2, 4, 8 and 16 weeks after immobilization and the expression patterns of TGF-beta1 and CTGF were characterized using in situ hybridization and immunohistochemistry.


RESULTS
The in situ hybridization demonstrated that the mRNAs of both TGF-beta1 and CTGF increased continuously during the first 2 weeks after immobilization and then decreased. The response was relatively higher in the posterior capsule than in the anterior one. In contrast, the immunoreactivity of both TGF-beta1 and CTGF increased gradually with time. The response was much stronger in the posterior capsule than in the anterior one.


CONCLUSIONS
The capsule has a potency to produce TGF-beta1 and CTGF after immobilization. CTGF may play a role in causing and maintaining capsular fibrosis in collaboration with TGF-beta1. The fibrotic change in the posterior capsule may have resulted in limited motion in extension in this immobilized knee model in rats. It may be possible to prevent joint contractures by somehow blocking the fibrotic process.
Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Japan 980-8574. hagi@mail.tains.tohoku.ac.jp
Yoshihiro
Y
Hagiwara
Eiichi
E
Chimoto
Ichiro
I
Takahashi
Akira
A
Ando
Yasuyuki
Y
Sasano
Eiji
E
Itoi
D000818:Animals; D001483:Base Sequence; D055513:Connective Tissue Growth Factor; D003286:Contracture / Q000517:prevention & control; D017931:DNA Primers; D017874:Immediate-Early Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D017746:Joint Capsule / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
C526316:CCN2 protein, rat; D017931:DNA Primers; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor