Effects of Ligustrazine on miR- 20b/VEGF and BMP 2/Smad1 Pathways in Subchondral Bone of Knee Osteoarthritis Model Rats
- VernacularTitle:川芎嗪对膝骨性关节炎大鼠软骨下骨中miR-20b/VEGF和BMP2/Smad1通路的影响
- Author:
Guihong LIANG
1
,
2
;
Zujian LIANG
3
;
Pingjin XIE
4
;
Jianke PAN
1
;
Lingfeng ZENG
1
,
2
;
Weiyi YANG
1
;
Hetao HUANG
1
;
Yanhong HAN
1
;
Jun LIU
1
Author Information
1. Dept. of Orthopedics，the Second Affiliated Hospital of Guangzhou University of TCM & Guangdong Provincial Hospital of TCM，Guangzhou 510120，China
2. Bone and Joint Research Team of Degeneration and Injury，Guangdong Provincial Academy of Chinese Medicinal Sciences，Guangzhou 510120，China
3. Dept. of Elder Orthopedics，the Third Affiliated Hospital of Guangzhou University of TCM，Guangzhou 510240，China
4. Dept. of Orthopedics，Shenzhen Luohu District Hospital of TCM & Shenzhen H ospital of Shanghai U niversity of TCM，Guangdong Shenzhen 518001，China
- Publication Type:Journal Article
- Keywords:
Ligustrazine;
Knee osteoarthritis;
Subchondral bone;
Rat;
miR-20b;
VEGF;
BMP;
Smad;
Mechanism
- From:
China Pharmacy
2019;30(4):448-453
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To study the effects of ligustrazine on miR-20b/VEGF and BMP2/Smad1 pathways in subchondral bone of knee osteoarthritis （KOA） model rats， and to investigate the mechanism of ligustrazine for KOA prevention and treatment. METHODS： Totally 18 healthy male SD rats were randomly divided into normal control group， model group and ligustrazine group， with 6 rats in each group. The rats in the latter two groups were used to establish KOA model by intra-articular injection of 4％ papain solution. From the 2nd day after the last injection， ligustrazine group was given intragastrical administration of Ligustrazine suspension （100 mg/kg） 2 mL； normal control group and model group were given intragastrical administration of isometrical normal saline， once a day， for consecutive 6 weeks. After the last after medication， the situation of bilateral knee articular cartilage of rats were observed after exposure. The knee joints of rats were sectioned and stained with HE. The pathological change of articular cartilage were observed by microscope and scored by modified Mankin’s score. mRNA expression of VEGF， BMP2 and Smad1， and the expression of miR-20b were detected by RT-PCR； the protein expression of VEGF， BMP2 and Smad1 were detected by Western blot assay. RESULTS： Model group and ligustrazine group suffered from cartilage injury of knee joint at varying degrees. Compared with normal control group， Mankin’s scores of knee joint and cartilage tissue were increased significantly in model group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone of model group were decreased significantly， while mRNA and protein expression of VEGF were increased significantly （P＜0.01）. Compared with model group， Mankin’s score of cartilage tissue were decreased significantly in ligustrazine group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone were increased significantly， while mRNA and protein expression of VEGF were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Ligustrazine can repair damaged articular cartilage in KOA model rats， the mechanism of which may be associated with inhibiting the protein expression of VEGF and activating BMP-2/Smad1 signaling pathway via up-regulating the expression of miR-20b， and promoting the degradation of VEGF mRNA in subchondral bone.
