Reduction of intraarticular adhesion of knee by local application of rapamycin in rabbits via inhibition of fibroblast proliferation and collagen synthesis.
BACKGROUND
The formation of intraarticular adhesion is a common complication after total knee arthroplasty or anterior cruciate ligament reconstruction. Previously, little research was reported regarding whether the local application of rapamycin (RAPA) could reduce intraarticular adhesion following knee surgery. In our present study, we determined the therapeutic effect of RAPA by local application on the reduction of intraarticular adhesion following knee surgery in rabbits.


METHODS
In this study, we built the model of knee surgery according to a previous study. The decorticated areas of the cortical bone were exposed and covered with cotton pads soaked with different concentrations of RAPA or physiological saline for 10 min. All of the rabbits were euthanized 4 weeks after the surgery. Macroscopic evaluation of the hydroxyproline content, the histological morphological analysis and collagen density and fibroblast density were used to evaluate the effect of RAPA on reducing intraarticular adhesion.


RESULTS
The results shown that RAPA could significantly inhibit the proliferation of fibroblasts and reduce collagen synthesis; in the rabbit model of knee surgery, there were weak scar tissues around the decorticated areas in the 0.2 mg/ml RAPA group; moderate scar tissues were found in the 0.1 mg/ml RAPA group. However, severe fibrous adhesions were found in the 0.05 mg/ml RAPA group and the control group. The hydroxyproline content and the fibroblast density in the 0.2 mg/ml and 0.1 mg/ml RAPA groups were significantly less than those of the control group.


CONCLUSIONS
We concluded that the local application of RAPA could reduce intraarticular adhesion after knee surgery in the rabbit model; this effect was mediated by inhibition of fibroblast proliferation and collagen synthesis, which may provide a new method for reducing intraarticular adhesion after clinical knee surgery.
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan, 410012, China.|Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Shuai
S
Zhao
Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Yu
Y
Sun
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan, 410012, China.|Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Xiaolei
X
Li
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan, 410012, China. jingchengwyz@163.com.|Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China. jingchengwyz@163.com.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China. jingchengwyz@163.com.
Jingcheng
J
Wang
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan, 410012, China. yanlianqi@126.com.|Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China. yanlianqi@126.com.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China. yanlianqi@126.com.
Lianqi
L
Yan
Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Hui
H
Chen
Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan, 410012, China.|Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Daxin
D
Wang
Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Jihang
J
Dai
Department of Orthopedics, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu, 225001, China.|Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, China.
Jun
J
He
D000287:Administration, Topical; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D011817:Rabbits; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
D007166:Immunosuppressive Agents; D003094:Collagen; D020123:Sirolimus
Collagen synthesis; Fibroblast; Intraarticular adhesion; Rapamycin