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维生素 D 通过 TGF-β1 信号对人关节软骨细胞蛋白聚糖的保护作用。

Protective Effects of Vitamin D on Proteoglycans of Human Articular Chondrocytes through TGF-β1 Signaling.

机构信息

Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.

Department of Orthopedic Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China.

出版信息

Nutrients. 2024 Sep 4;16(17):2991. doi: 10.3390/nu16172991.

Abstract

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes.

摘要

软骨的细胞外基质主要由胶原和聚集蛋白聚糖构成。骨关节炎(OA)中软骨的降解始于聚集蛋白聚糖的丢失。维生素 D(VD)在几种与炎症相关的疾病中发挥着重要作用,并且可以在 OA 期间保护软骨中的胶原。本研究主要关注 VD 在 TNF-α(TNF-α)处理的人关节软骨细胞中聚集蛋白聚糖周转中的作用及其可能的机制。研究了不同剂量的 VD 和不同时期的 TNF-α和 TGF-β1 受体(TGFβR1)抑制剂 SB525334 干预的作用。测量了人软骨细胞的活力和 TGF-β1 的细胞外分泌。检查了细胞内 TGFβR1 和 VD 受体的表达。分析了聚集蛋白聚糖及其相关代谢因子的转录和翻译水平。结果表明,TNF-α显著降低了人软骨细胞的活力、TGFβR1 表达和聚集蛋白聚糖水平,增加了解整合素和金属蛋白酶与血小板反应蛋白基序。VD 处理部分抑制了这些变化。此外,在 TNF-α处理的细胞中,TGFβR1 抑制剂 SB525334 阻断了 VD 的作用。VD 可能通过人软骨细胞中的 TGF-β1 信号通路预防 TNF-α引起的蛋白聚糖丢失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2377/11396982/f302b2ca8eb5/nutrients-16-02991-g001.jpg

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