Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels

Juan Xu,Xiaoguang Chen,Zhitao Feng,Junqing Zhu,Shixian Chen,Xianghui Wu,Juan Li

doi:10.1007/s10067-017-3646-1

Juan Xu, Xiaoguang Chen + Show 5 more

Open Access

https://doi.org/10.1007/s10067-017-3646-1

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Abstract

The objective of the present study is to evaluate the inhibitory effects of taxol (PTX) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. Collagen II (C II) and complete Freund’s adjuvant (CFA) were used in C57BL/6 (H-2b) mice to generate the CIA model. Random grouping was performed in the normal control group, CIA model group, PTX 1.5 mg/kg group, PTX 1.0 mg/kg group, and PTX 0.5 mg/kg group. Arthritis index scores, tissue pathology scores, and synovium microvessel density (MVD) analysis were performed. Immunohistochemistry and enzyme-linked immunosorbent assay were used to detect the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-α (HIF-1α). The correlation between MVD and pathological scores and between MVD and the expression of VEGF as well as HIF-1α in the synovium were also evaluated. After PTX treatment, the three intervention group arthritis index scores were reduced when compared with the CIA group. The total histological scores in the three PTX treatment groups were lower than those in the CIA group. Similarly, PTX significantly alleviated the scores for synovitis, pannus formation, and bone destruction. Compared with the CIA group, the MVD of the three intervention groups decreased in a dose-dependent manner. The expression of VEGF and HIF-1α in synovial tissues and serum also significantly decreased after PTX treatment. Further analysis showed that MVD and pathological scores and MVD and expression of VEGF as well as HIF-1α in the synovium were positively correlated. PTX may alleviate CIA by suppressing angiogenesis, providing new insights into the treatment of rheumatoid arthritis (RA). VEGF and HIF-1α may be targets for PTX suppression of microvessel formation.

Highlights

Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease that is characterized by persistent synovitis and angiogenesis, resulting in synovial hyperplasia and progressive destruction of bone and cartilage [1,2,3]
The expression of CD31 was detected by immunohistochemistry to measure the Effect of PTX on the clinical manifestation and arthritis index of collagen-induced arthritis (CIA) mice No significant differences in arthritis scores were observed between the three PTX treatment groups and the CIA group before the PTX intervention
The current study demonstrated that PTX treatment alleviated CIA arthritis scores, as evidenced by the reduction of erythema and swelling

Summary

Introduction

Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease that is characterized by persistent synovitis and angiogenesis, resulting in synovial hyperplasia and progressive destruction of bone and cartilage [1,2,3]. A vast body of research has indicated that angiogenesis is involved in the pathogenesis of RA [6]. It is involved in several physiological events such as inflammation, embryonic organ development, tissue repair, reproduction, and wound healing [7]. In RA, uncontrolled neovascularization can induce synovial hyperplasia and progressive bone destruction by fostering the infiltration of inflammatory cells into the joints, which promotes the process

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