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15-Lipoxygenase-1 in osteoblasts promotes TGF-β1 expression via inhibiting autophagy in human osteoarthritis.

成骨细胞中 15-Lipoxygenase-1 通过抑制人骨关节炎中自噬促进tgf-β 1 的表达。

  • 影响因子:3.78
  • DOI:10.1016/j.biopha.2019.109548
  • 作者列表:"Wan Y","Lv Y","Li L","Yin Z
  • 发表时间:2020-01-01
Abstract

BACKGROUND:15-Lipoxygenase-1 (15-LOX-1) belongs to the lipoxygenase family involved in the inflammatory response and pathological process of various diseases, including osteoarthritis (OA). The overexpression of TGF-β1 in osteoblasts leads to abnormal changes in subchondral bone structure, eventually causing OA. However, the pathogenesis of the disease is poorly defined, and the interaction between 15-LOX-1 and TGF-β1 in osteoblasts has not been evaluated in OA. In this study, the role of 15-LOX-1 in subchondral bone osteoblasts in OA was evaluated. METHOD:15-LOX-1 expression in osteoblasts of the subchondral bone of patients with OA was measured by immunohistochemistry, qRT-PCR, and western blotting. Osteoblasts extracted from the subchondral bone of OA were transfected with 15-LOX-1 siRNA and an overexpression vector. The eff ;ect of 15-LOX-1 on the expression of TGF-β1 in OA osteoblasts was assessed by qRT-PCR and western blotting. The effect of 15-LOX-1 on autophagy via AMPK pathway in OA osteoblasts was evaluated by qRT-PCR, western blotting, and transmission electron microscopy. RESULTS:The expression levels of 15-LOX-1 and TGF-β1 were higher in OA subchondral bone osteoblast than that in non-OA subchondral bone. 15-LOX-1, which downregulated autophagy by inhibiting AMPK following the activation of mTORC1, upregulated the osteoblast expression of TGF-β1. Treatment with autophagy inhibitors significantly increased the expression levels of TGF-β1 in osteoblasts. CONCLUSION:In the present study, our findings suggested that 15-Lipoxygenase-1 in Osteoblasts Promotes TGF-β1 expression via inhibiting autophagy in human Osteoarthritis. These novel results suggested that 15-Lipoxygenase-1 expressed by subchondral bone osteoblasts might be a promising therapeutic target in human OA.

摘要

背景: 1 5-脂氧合酶-1 (1 5-LOX-1) 属于脂氧合酶家族,参与多种疾病的炎症反应和病理过程,包括骨关节炎 (OA)。成骨细胞中tgf-β 1 的过度表达导致软骨下骨结构的异常改变,最终引起OA。然而,该病的发病机制尚不明确,1 5-LOX-1 和TGF-β 1 在成骨细胞中的相互作用尚未在OA中得到评价。本研究评价了 1 5-LOX-1 在OA软骨下骨成骨细胞中的作用。 方法: 采用免疫组织化学、qRT-PCR和western blotting检测OA患者软骨下骨成骨细胞中 1 5-LOX-1 的表达。用 1 5-LOX-1 siRNA和过表达载体转染从OA软骨下骨中提取的成骨细胞。通过qRT-PCR和western blotting评估 1 5-LOX-1 对OA成骨细胞TGF-β 1 表达的影响。通过qRT-PCR、western blotting和透射电镜评价 1 5-LOX-1 通过AMPK通路对OA成骨细胞自噬的影响。 结果: 1 5-LOX-1 和TGF-β 1 在OA软骨下骨成骨细胞中的表达水平高于非OA软骨下骨。1 5-LOX-1 通过抑制mTORC 1 激活后的AMPK下调自噬,上调TGF-β 1 的成骨细胞表达。自噬抑制剂治疗可显著增加成骨细胞中tgf-β 1 的表达水平。 结论: 在本研究中,我们的研究结果表明成骨细胞中的 15-Lipoxygenase-1 通过抑制人骨关节炎中的自噬促进tgf-β 1 的表达。提示软骨下骨成骨细胞表达的 15-Lipoxygenase-1 有望成为治疗OA的新靶点。

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影响因子:4.13
发表时间:2020-01-01
DOI:10.1002/acr.23824
作者列表:["Chen SK","Liao KP","Liu J","Kim SC"]

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影响因子:4.13
发表时间:2020-01-01
DOI:10.1002/acr.23827
作者列表:["Lee RR","Rashid A","Thomson W","Cordingley L"]

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关节疾病方向

各类骨关节疾病,包括退行性关节炎、滑囊炎、滑膜炎、颈椎病、腰椎病、肩周炎、骨质增生、风湿性关节炎、类风湿性关节炎、股骨头坏死等。

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