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血管内皮生长因子受骨关节炎患者滑膜成纤维细胞中经典和非经典转化生长因子-β 通路的调节。

Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor- Pathway in Synovial Fibroblasts Derived from Osteoarthritis Patients.

机构信息

Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku, Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.

Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Minami-ku, Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.

出版信息

Biomed Res Int. 2019 Sep 29;2019:6959056. doi: 10.1155/2019/6959056. eCollection 2019.

DOI:10.1155/2019/6959056
PMID:31662989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6791277/
Abstract

BACKGROUND

Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGF). However, the signaling pathway governing TGF-mediated regulation of VEGF in SFs has not been identified.

METHODS

OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGF (hrTGF), hrTGF + ALK5 inhibitor SB505124, hrTGF + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGF + p38 inhibitor SB203580 for 6 h. mRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting.

RESULTS

ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGF-induced mRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGF-mediated mRNA and VEGF protein production.

CONCLUSION

TGF-mediated regulation of expression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway.

摘要

背景

先前的研究表明，血管内皮生长因子 (VEGF) 的存在与膝骨关节炎 (OA) 患者的 OA 严重程度和疼痛有关。转化生长因子-β (TGF) 可诱导人滑膜成纤维细胞 (SF) 中 VEGF 的表达。然而，调控 TGF 介导的 SF 中 VEGF 表达的信号通路尚未确定。

方法

接受全膝关节置换术的 OA 患者提取滑膜组织 (SYT) 并培养其组成的 SF。用培养基 (对照)、人重组 TGF (hrTGF)、hrTGF+ALK5 抑制剂 SB505124、hrTGF+转化生长因子激活激酶 1 (TAK1) 抑制剂 (5Z)-7-氧杂-zeaenol 或 hrTGF+p38 抑制剂 SB203580 刺激细胞 6 小时。使用实时聚合酶链反应检测 SF 中的 mRNA 表达，并使用酶联免疫吸附试验检测细胞上清液中的 VEGF 蛋白产生。此外，使用 Western blot 检测 SMAD2 和 p38 的磷酸化水平。

结果

ALK5 (SB505124) 和 TAK1 (5Z-oxozeaenol) 抑制剂完全抑制 TGF 诱导的 mRNA 表达和 VEGF 蛋白产生。SB505124 和 5Z-oxozeaenol 也抑制了 SMAD2 和 p38 的磷酸化。p38 抑制剂 (SB203580) 部分抑制了 TGF 介导的 mRNA 和 VEGF 蛋白产生。

结论

TGF 介导的 OA 患者 SYT 中 表达和 VEGF 蛋白产生的调节通过经典和非经典途径发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/7df9ef3caba0/BMRI2019-6959056.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/f78ab8957801/BMRI2019-6959056.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/05fc7ac1d665/BMRI2019-6959056.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/b073f731fdc4/BMRI2019-6959056.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/7df9ef3caba0/BMRI2019-6959056.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/f78ab8957801/BMRI2019-6959056.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/05fc7ac1d665/BMRI2019-6959056.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/b073f731fdc4/BMRI2019-6959056.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e6/6791277/7df9ef3caba0/BMRI2019-6959056.004.jpg

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3
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4
Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.细胞焦亡：退行性骨与关节疾病中细胞和平共处的破坏者
J Adv Res. 2025 May;71:227-262. doi: 10.1016/j.jare.2024.06.010. Epub 2024 Jun 13.
5
Adult fibroblasts use aggresomes only in distinct cell-states.成纤维细胞仅在特定细胞状态下使用聚集物。
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