Activation of STAT3 (signal transducer and activator of transcription 3) in synovial tissues from the hip joint in the early stage of rapidly destructive coxopathy.

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Tadashi Yasuda, Shigeo Hara, Shinnosuke Yamashita, Sadaki Mitsuzawa, Yoshihiro Tsukamoto, Hisataka Takeuchi, Satoshi Ota, Eijiro Onishi
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引用次数: 0

Abstract

Interleukin-6 signaling activates signal transducer and activator of transcription 3 (STAT3), resulting in matrix metalloproteinase-3 (MMP-3) production. The hip joints with rapidly destructive coxopathy (RDC) show rapid chondrolysis, probably by increased MMP-3. This study aimed to elucidate STAT3 activation in the synovial tissues with joint destruction in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues demonstrated the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 activation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of the macrophage or T cell marker. Treatment with CP690,550, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of CP690,550 could work through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Thus, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.

快速破坏性髋关节病早期髋关节滑膜组织中STAT3(信号换能器和转录激活因子3)的激活
白细胞介素-6信号传导激活信号转导因子和转录激活因子3 (STAT3),导致基质金属蛋白酶-3 (MMP-3)的产生。快速破坏性髋关节病(RDC)表现为快速软骨松解,可能是由MMP-3升高引起的。本研究旨在阐明STAT3在RDC早期关节破坏滑膜组织中的激活。从4例股骨头破坏和血清MMP-3高水平的RDC患者中获得疾病发病后7个月内的滑膜组织。RDC滑膜组织表现为滑膜内膜增生,cd68阳性巨噬细胞和cd3阳性T淋巴细胞增多。使用抗磷酸化STAT3抗体免疫组化发现滑膜组织中STAT3活化。大部分磷酸化- stat3阳性细胞为滑膜衬里细胞,巨噬细胞或T细胞标记物呈阴性表达。用一种Janus激酶抑制剂cp690550治疗,导致磷酸化STAT3阳性细胞减少,特别是高强度,表明有效抑制了RDC滑膜组织中STAT3的激活。cp690550的抑制作用可能通过RDC早期滑膜组织中的Janus激酶/STAT3轴起作用。因此,STAT3可能是预防RDC关节结构损伤的潜在治疗靶点。
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来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
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