Efficient inhibition of the formation of joint adhesions by ERK2 small interfering RNAs.
Transforming growth factor-beta1 and fibroblast growth factor-2 play very important roles in fibroblast proliferation and collagen expression. These processes lead to the formation of joint adhesions through the SMAD and MAPK pathways, in which extracellular signal-regulated kinase (ERK)2 is considered to be crucial. Based on these theories, we examined the effects of a lentivirus-mediated small interfering RNA (siRNA) targeting ERK2 on the suppression of joint adhesion formation in vivo. The effects were assessed in vivo from different aspects including the adhesion score, histology and joint contracture angle. We found that the adhesions in the ERK2 siRNA group became soft and weak, and were easily stretched. Accordingly, the flexion contracture angles in the ERK2 siRNA group were also reduced (P<0.05 compared with the control group). The animals appeared healthy, with no signs of impaired wound healing. In conclusion, local delivery of a lentivirus-mediated siRNA targeting ERK2 can ameliorate joint adhesion formation effectively and safely.
Li
Fengfeng
F
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai 200233, China.
Ruan
Hongjiang
H
Fan
Cunyi
C
Zeng
Bingfang
B
Wang
Chunyang
C
Wang
Xiang
X
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007592:Joint Diseases / Q000473:pathology / Q000517:prevention & control*; D007596:Joints / Q000201:enzymology* / Q000473:pathology; D016086:Lentivirus; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control
D034741:RNA, Small Interfering; D019950:Mitogen-Activated Protein Kinase 1