Study on the Therapeutic Effect of Lenalidomide on Hemophilic Arthropathy.
10.19746/j.cnki.issn.1009-2137.2022.05.038
- Author:
Ye-Fan WANG
1
;
Zhen-Yang LIN
1
;
Fei-Xu ZHANG
1
;
Xin-Yue ZHOU
1
;
Xia WU
1
;
Xiao XIAO
2
;
Jun-Jiang SUN
2
;
Bao-Lai HUA
3
,
4
Author Information
1. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
2. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China State Key Laboratory of Bioengineering, East China University of Science and Technology, Shanghai 200237, China.
3. Yangzhou Clinical College of Xuzhou Medical University, Yangzhou 225001, Jiangsu Province, China
4. Department of Hematology, Clinical School of Yangzhou University, Yangzhou 225001, Jiangsu Province, China.E-mail: baolaihua@hotmail. com.
- Publication Type:Journal Article
- Keywords:
hemophilia arthropathy;
human fibroblast-like synovial cells;
lenalidomide;
pro-inflammatory cytokines
- MeSH:
Animals;
Arthritis;
Cytokines/metabolism*;
Hemarthrosis/pathology*;
Hemophilia A/genetics*;
Humans;
Interleukin-6;
Lenalidomide;
Mice;
Neovascularization, Pathologic;
RNA, Messenger;
Sincalide;
Tumor Necrosis Factor-alpha;
Vascular Endothelial Growth Factor A
- From:
Journal of Experimental Hematology
2022;30(5):1549-1556
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effect of lenalidomide on human fibroblast-like synovial cells (HFLS) and the therapeutic efficacy on hemophilic arthropathy in hemophilia A mice model.
METHODS:In vitro, to remodel the inflammatory environment of synovial tissue after hemorrhage, ferric citrate and recombinant TNF-α were added into the cell culture medium of HFLS. Cell Counting Kit-8 (CCK-8), Enzyme-linked immunosorbent assay (ELISA), Quantitative Real-time PCR (RT-qPCR) and flow cytometry were employed for detection of the effects of lenalidomide on the proliferation ability, pro-inflammatory cytokines release and apoptosis of HFLS cells. In vivo, hemophilia arthropathy was remodeled in hemophilia A mice by induction of hemarthrosis. A series of doses of lenalidomide (0.1, 0.3 and 1.0 g/kg) was administrated intra-articularly. Tissues of knee joints were collected on the 14th day after administration, and the protective effect of lenalidomide on arthritis in hemophilia A mice were evaluated by RT-qPCR and histological grading.
RESULTS:In vitro, compared with the untreated control group, lenalidomide could significantly inhibit the proliferation of HFLS cells (P<0.05), and the effect was the most significant when the concentration was 0.01 μmol/L (P<0.001). Compared with the control group, lenalidomide could significantly inhibit the expression levels of TNF-α, IL-1β, IL-6 and IFN-γ in HFLS cells (P<0.05). The flow cytometry results showed that lenalidomide could enhance the apoptotis of HFLS cells (P<0.05). The results of RT-qPCR showed that lenalidomide could significantly reduce the mRNA expression levels of TNF-α, IL-1β, IL-6,MCP-1 and VEGF in the joint tissues (P<0.05). Histological results showed that compared with the injured group, lenalidomide could significantly reduce the pathological sequela after hemarthrosis induction, e.g. synovial thickening and neo-angiogenesis in the synovium. The protection displayed a dose-response pattern roughly.
CONCLUSION:In vitro, lenalidomide can inhibit the proliferation of HFLS cells, promote their apoptosis, and inhibit the expression of pro-inflammatory cytokines. In vivo, lenalidomide can significantly decrease the expression of pro-inflammatory cytokines in the joints of mice, and prevent the development of inflammation and neo-angiogenesis. The results provide a theoretical and experimental basis for the clinical application of lenalidomide in the treatment of hemophilic arthropathy.
