Syndecan-4 inhibition attenuates cartilage degeneration in temporomandibular joint osteoarthritis

IF 3.1 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of oral rehabilitation Pub Date : 2024-08-05 DOI:10.1111/joor.13829

Xiaohua Chen, Feng He, Hongyun Zhang, Yuanjun Ma, Jia Yu, Han Qin, Fan Wu, Zhuo Wang, Ying Zhan, Jing Zhang, Lei Lu, Mian Zhang, Shibin Yu

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引用次数: 0

Abstract

Background

Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix.

Objective

This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA).

Methods

Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1β (rrIL-1β) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4^flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays.

Results

SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition.

Conclusions

SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.

Abstract Image

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抑制 Syndecan-4 可减轻颞下颌关节骨关节炎的软骨退化。

背景：Syndecan 4（SDC4）是一种I型跨膜蛋白多糖，是连接软骨细胞和细胞外基质的关键纽带：本研究旨在探讨SDC4在颞下颌关节骨性关节炎（TMJOA）软骨退化中的作用：方法：用不同浓度的重组大鼠白细胞介素-1β（rrIL-1β）和 SDC4 小干扰 RNA（si-SDC4）刺激髁状突软骨细胞。在 TMJOA 模型大鼠的关节内注射抗 SDC4 外域特异性抗体或 IgG。诱导 SDC4 条件性基因敲除（SDC4-cKO）和 Sdc4flox/flox 小鼠颞下颌关节损伤。使用血红素和伊红（H&E）以及安全素 O（SO）染色评估软骨退化情况。通过免疫组织化学（IHC）染色或 Western 印迹检测评估了髁状突软骨中 SDC4、基质金属蛋白酶（MMPs）、具有血栓软骨蛋白基序的分解蛋白和金属蛋白酶 5（ADAMTS5）、肿瘤坏死因子α（TNFα）、II 型胶原（Col-II）、凝集素（ACAN）、裂解的 Caspase 3（CASP3）、Ki67 和相关通路的蛋白水平：rrIL-1β刺激增加了软骨细胞中SDC4、MMP3和ADAMTS5的表达，同时降低了Col-II的表达。这些效应在体外被 si-SDC4 逆转。在体内，阻断 SDC4 可减少软骨细胞的死亡和软骨基质的损失，这体现在 Col-II 和 ACAN 的表达增加，以及 SDC4、MMP13 和裂解-CASP3 阳性细胞的减少。此外，抑制 SDC4 后，ACAN 和 Ki67 蛋白水平升高，ERK1/2 和 P38 信号通路被激活：结论：抑制 SDC4 能明显改善髁状突软骨退化，这至少部分是通过 P38 和 ERK1/2 信号传导介导的。抑制 SDC4 可能对治疗颞下颌关节损伤具有重要价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of oral rehabilitation 医学-牙科与口腔外科

CiteScore

5.60

自引率

10.30%

发文量

116

审稿时长

4-8 weeks

期刊介绍： Journal of Oral Rehabilitation aims to be the most prestigious journal of dental research within all aspects of oral rehabilitation and applied oral physiology. It covers all diagnostic and clinical management aspects necessary to re-establish a subjective and objective harmonious oral function. Oral rehabilitation may become necessary as a result of developmental or acquired disturbances in the orofacial region, orofacial traumas, or a variety of dental and oral diseases (primarily dental caries and periodontal diseases) and orofacial pain conditions. As such, oral rehabilitation in the twenty-first century is a matter of skilful diagnosis and minimal, appropriate intervention, the nature of which is intimately linked to a profound knowledge of oral physiology, oral biology, and dental and oral pathology. The scientific content of the journal therefore strives to reflect the best of evidence-based clinical dentistry. Modern clinical management should be based on solid scientific evidence gathered about diagnostic procedures and the properties and efficacy of the chosen intervention (e.g. material science, biological, toxicological, pharmacological or psychological aspects). The content of the journal also reflects documentation of the possible side-effects of rehabilitation, and includes prognostic perspectives of the treatment modalities chosen.