Heparan sulfate functions are altered in the osteoarthritic cartilage.
Heparan sulfate functions are altered in the osteoarthritic cartilage.
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DOI：
10.1186/s13075-020-02352-3
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发表时间：
2020-12-07
影响因子：
4.9
通讯作者：
Albanese P
中科院分区：
文献类型：
--
作者：
Shamdani S;Chantepie S;Flageollet C;Henni-Chebra N;Jouan Y;Eymard F;Hay E;Cohen-Solal M;Papy-Garcia D;Chevalier X;Albanese P
硫酸乙酰肝素（HS）蛋白聚糖（PG）可在软骨细胞表面和细胞周软骨基质中发现，并参与细胞-细胞和细胞-基质相互作用。HS链的一个重要功能是通过与肝素结合蛋白（HBP）的特异性相互作用调节细胞命运，HBP由其复杂的硫酸化模式调节。骨关节炎（OA）是一种以关节软骨细胞外基质降解为特征的关节疾病。本研究的目的是调查HS的结构和功能在骨关节炎软骨相比，正常软骨（对照）。从人肉眼正常软骨（对照，n = 7）和（OA软骨n = 11）中提取糖胺聚糖（GAG）。分离HS并使用DMMB定量方法进行定量。分别用HPLC分析和HBP结合试验比较了它们的结构和功能，并用RQ-PCR研究了它们对小鼠软骨细胞的表型影响。使用单因素ANOVA进行统计分析，然后进行Dunnett检验或t检验进行成对比较。在OA中，HS的特征在于与对照组相比硫酸化水平增加。此外，这些HS结合参与OA病理生理过程的HBP如FGF 2和VEGF的能力降低。硫酸软骨素和硫酸角质素调节这些结合特性。最后，来自OA软骨的HS诱导小鼠关节软骨细胞中分解代谢标志物如MMP 3、MMP 13和TS 4的mRNA水平，并抑制合成代谢标志物如COL 2、ACAN、SOX 9和VEGF的mRNA水平。在OA软骨中HS链的硫酸化随着HBP结合特性和对软骨细胞表型的生物学效应的变化而增加。因此，存在于改变的软骨中的改良HS可能是OA的新治疗靶点。
Heparan sulfate (HS) proteoglycans (PG) may be found at the chondrocyte surface and in the pericellular cartilage matrix, and are involved in cell-cell and cell-matrix interactions. An important function of HS chains is to regulate cell fate through specific interactions with heparin-binding proteins (HBP) modulated by their complex sulfation pattern. Osteoarthritis (OA) is a joint disorder characterized by the degradation of articular cartilaginous extracellular matrix. The aim of this study was to investigate HS structure and functions in osteoarthritic cartilages compared to normal cartilages (controls). Glycosaminoglycans (GAG) were extracted from human macroscopically normal cartilages (controls, n = 7) and (OA cartilages n = 11). HS were isolated and quantified using the DMMB quantification method. Their structure and functions were then compared using respectively a HPLC analysis and HBP binding tests and their phenotypic effects on murine chondrocytes were studied by RQ-PCR. Statistical analyzes were performed using a one-way ANOVA followed by a Dunnett’s test or a t test for pairwise comparisons. In OA, HS were characterized by increased sulfation levels compared to controls. Moreover, the capacity of these HS to bind HBP involved in the OA pathophysiological process such as FGF2 and VEGF was reduced. Chondroitin sulfates and keratan sulfates regulated these binding properties. Finally, HS from OA cartilages induced the mRNA levels of catabolic markers such as MMP3, MMP13, and TS4 and inhibited the mRNA levels of anabolic markers such as COL2, ACAN, SOX9, and VEGF in murine articular chondrocytes. The sulfation of HS chains was increased in OA cartilages with changes in HBP binding properties and biological effects on chondrocyte phenotypes. Thus, modified HS present in altered cartilages could be a novel therapeutic target in OA.
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影响因子：
15.9
作者：
Lark, MW;Bayne, EK;Lohmander, LS
通讯作者：
Lohmander, LS
影响因子：
13.3
作者：
Funck-Brentano, Thomas;Bouaziz, Wafa;Cohen-Solal, Martine
通讯作者：
Cohen-Solal, Martine
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
7
作者：
Kirsch, T;Swoboda, B;Nah, HD
通讯作者：
Nah, HD
影响因子：
4
作者：
Ellman, M. B.;Yan, D.;Ahmadinia, K.;Chen, D.;An, H. S.;Im, H. J.
通讯作者：
Im, H. J.