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鉴定关节软骨中表达 CD163 的吞噬性软骨细胞及其在软骨降解中的新型清道夫作用。

The identification of CD163 expressing phagocytic chondrocytes in joint cartilage and its novel scavenger role in cartilage degradation.

机构信息

Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.

出版信息

PLoS One. 2013;8(1):e53312. doi: 10.1371/journal.pone.0053312. Epub 2013 Jan 11.

Abstract

BACKGROUND

Cartilage degradation is a typical characteristic of arthritis. This study examined whether there was a subset of phagocytic chondrocytes that expressed the specific macrophage marker, CD163, and investigated their role in cartilage degradation.

METHODS

Cartilage from the knee and temporomandibular joints of Sprague-Dawley rats was harvested. Cartilage degradation was experimentally-induced in rat temporomandibular joints, using published biomechanical dental methods. The expression levels of CD163 and inflammatory factors within cartilage, and the ability of CD163(+) chondrocytes to conduct phagocytosis were investigated. Cartilage from the knees of patients with osteoarthritis and normal cartilage from knee amputations was also investigated.

RESULTS

In the experimentally-induced degrading cartilage from temporomandibular joints, phagocytes were capable of engulfing neighboring apoptotic and necrotic cells, and the levels of CD163, TNF-α and MMPs were all increased (P<0.05). However, the levels of ACP-1, NO and ROS, which relate to cellular digestion capability were unchanged (P>0.05). CD163(+) chondrocytes were found in the cartilage mid-zone of temporomandibular joints and knee from healthy, three-week old rats. Furthermore, an increased number of CD163(+) chondrocytes with enhanced phagocytic activity were present in Col-II(+) chondrocytes isolated from the degraded cartilage of temporomandibular joints in the eight-week experimental group compared with their age-matched controls. Increased number with enhanced phagocytic activity of CD163(+) chondrocytes were also found in isolated Col-II(+) chondrocytes stimulated with TNF-α (P<0.05). Mid-zone distribution of CD163(+) cells accompanied with increased expression of CD163 and TNF-α were further confirmed in the isolated Col-II(+) chondrocytes from the knee cartilage of human patients with osteoarthritis, in contrast to the controls (both P<0.05).

CONCLUSIONS

An increased number of CD163(+) chondrocytes with enhanced phagocytic activity were discovered within degraded joint cartilage, indicating a role in eliminating degraded tissues. Targeting these cells provides a new strategy for the treatment of arthritis.

摘要

背景

软骨降解是关节炎的一个典型特征。本研究探讨了是否存在表达特定巨噬细胞标志物 CD163 的吞噬性软骨细胞亚群,并研究了它们在软骨降解中的作用。

方法

从 Sprague-Dawley 大鼠的膝关节和颞下颌关节中采集软骨。使用已发表的生物力学牙科方法,在大鼠颞下颌关节中实验性诱导软骨降解。研究了软骨内 CD163 和炎症因子的表达水平,以及 CD163(+)软骨细胞吞噬的能力。还研究了骨关节炎患者膝关节的软骨和膝关节截肢的正常软骨。

结果

在实验性降解的颞下颌关节软骨中,吞噬细胞能够吞噬邻近的凋亡和坏死细胞,CD163、TNF-α 和 MMPs 的水平均升高(P<0.05)。然而,与细胞消化能力相关的 ACP-1、NO 和 ROS 水平不变(P>0.05)。在健康、三周大的大鼠的颞下颌关节和膝关节的软骨中层发现了 CD163(+)软骨细胞。此外,在 8 周实验组降解的颞下颌关节软骨中,与年龄匹配的对照组相比,Col-II(+)软骨细胞中存在更多具有增强吞噬活性的 CD163(+)软骨细胞。在 TNF-α刺激的 Col-II(+)软骨细胞中也发现了更多具有增强吞噬活性的 CD163(+)软骨细胞(P<0.05)。在骨关节炎患者膝关节软骨的 Col-II(+)软骨细胞中进一步证实了 CD163(+)细胞的中层分布以及 CD163 和 TNF-α的表达增加,与对照组相比(均 P<0.05)。

结论

在降解的关节软骨中发现了具有增强吞噬活性的更多 CD163(+)软骨细胞,表明其在清除降解组织中起作用。针对这些细胞为关节炎的治疗提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d0f/3543453/cd53acc5412e/pone.0053312.g001.jpg

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