Weekly injections of Hylan G-F 20 delay cartilage degeneration in partial meniscectomized rat knees.
BACKGROUND
Cross-linked hyaluronan--also called Hylan G-F 20--is a medical device developed to treat osteoarthritis of the knee. However, it is still controversial whether Hylan G-F 20 has a cartilage protective effect in trauma-induced osteoarthritis. We investigated whether Hylan G-F 20 delayed osteoarthritis progression in a partial meniscectomized rat model.


METHODS
Lewis rats were used for the experiments. The anterior medial meniscus was resected at the level of the medial collateral ligament in both knees. From 1 week after the surgery, 50 μl of Hylan G-F 20 was injected weekly into the left knee and phosphate buffered saline was injected into the right knee. Cartilage was evaluated for macroscopic findings, histology with safranin-o, and expression of type II collagen at 2, 4, and 8 weeks. Synovitis was also evaluated, and immunohistochemical analysis was performed for ED1.


RESULTS
Macroscopic findings demonstrated that India ink positive area, representing fibrillated cartilage, was significantly smaller in the Hylan G-F 20 group than in the control group at 2, 4, and 8 weeks (n = 5). There were no significant differences in osteophyte score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks. Histologically, the cartilage in the medial tibial plateau was destroyed at 8 weeks in the control group, while type II collagen expression was still observed at 8 weeks in the Hylan G-F 20 group. OARSI score for cartilage histology was significantly lower in the Hylan G-F 20 group than in the control group at 4 and 8 weeks (n = 5). There were no significant differences in synovial cell number or modified synovitis score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks (n = 5). In the Hylan G-F 20 group, foreign bodies surrounded by ED1 positive macrophages were observed in the synovium.


CONCLUSIONS
Weekly injections of Hylan G-F 20 starting 1 week after surgery delayed cartilage degeneration after meniscectomy in a rat model. Synovitis induced by meniscectomy was not alleviated by Hylan G-F 20. Insoluble gels were observed in the synovium after the Hylan G-F 20 injection.
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Katsuaki
K
Yanagisawa
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Takeshi
T
Muneta
Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Nobutake
N
Ozeki
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Yusuke
Y
Nakagawa
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Mio
M
Udo
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Ryusuke
R
Saito
Department of Joint Surgery and Sports Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Hideyuki
H
Koga
Department of Cartilage Regeneration, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Kunikazu
K
Tsuji
Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. sekiya.arm@tmd.ac.jp.
Ichiro
I
Sekiya
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D002357:Cartilage Diseases / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D004334:Drug Administration Schedule; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008297:Male; D008592:Menisci, Tibial / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew
D001672:Biocompatible Materials; C049816:hylan; D006820:Hyaluronic Acid
Hyaluronan; Hylan G-F 20; Osteoarthritis; Partial meniscectomy; Rat