Silencing of miR-101 Prevents Cartilage Degradation by Regulating Extracellular Matrix-related Genes in a Rat Model of Osteoarthritis.
Osteoarthritis (OA) is a common, degenerative joint disease characterized by articular cartilage degradation. Currently, clinical trials based on microRNA therapy have been performed to treat various diseases. However, no treatment has been found for arthritis. This study investigated the functions of miR-101 in cartilage degradation in vivo and evaluated the feasibility of using miR-101 as a therapeutic agent for OA. Mono-iodoacetate-induced arthritis (MIA) rats were used as an animal model of OA. miR-101 mimic or miR-101 inhibitor was injected into the rats' knees to evaluate its effects on cartilage degradation. Cartilage degradation aggravated at 14 days after the injection of miR-101 mimic. By contrast, miR-101 silencing reduced cartilage degradation. Moreover, the administration of miR-101 mimic is sufficient to cause cartilage degradation in the normal cartilage of rats. By contrast, miR-101 inhibitor could prevent this change. Microarray and qPCR were used to investigate the different expressed genes after injecting miR-101 mimic and miR-101 inhibitor in the rats' articular cartilage. Several cartilage degradation-related genes were selected and validated to function in cartilage degradation with miR-101. Our results demonstrated the therapeutic effect of miR-101 inhibition on cartilage degradation in MIA rats by regulating several cartilage degradation-related genes.
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China; Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing, P. R. China.
Linghui
L
Dai
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Xin
X
Zhang
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Xiaoqing
X
Hu
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Qiang
Q
Liu
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Zhentao
Z
Man
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Hongjie
H
Huang
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China.
Qingyang
Q
Meng
Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing, P. R. China. Electronic address: chunyanzhou@bjmu.edu.cn.
Chunyan
C
Zhou
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P. R. China. Electronic address: yingfang.ao@gmail.com.
Yingfang
Y
Ao
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000628:therapy; D002358:Cartilage, Articular / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D020868:Gene Silencing; D005822:Genetic Vectors; D007461:Iodoacetates / Q000737:chemistry; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
D016207:Cytokines; D007461:Iodoacetates; C579142:MIRN101 microRNA, rat; D035683:MicroRNAs; D055758:SOX9 Transcription Factor