Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of the knee
Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of the knee
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DOI：
10.1016/j.joca.2013.11.010
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发表时间：
2014-02-01
影响因子：
7
通讯作者：
Matsumoto, K.
中科院分区：
文献类型：
--
作者：
Ishimaru, D.;Sugiura, N.;Matsumoto, K.
目的：为了确定软骨中的硫酸软骨素（CS）的结构是否反映了膝关节骨关节炎（OA）患者的软骨退化程度，并确定CS生物合成如何影响软骨degeneration.Design：从24个终末期OA膝关节的内侧股骨髁（MFC）和外侧股骨髁（LFC）获得两个骨关节炎软骨样本。将样本分为两组：病变软骨和远端软骨分别与骨关节炎软骨相邻和远离。根据Mankin评分确定组织学分级。CS浓度和链长分别采用高效液相色谱法（HPLC）和凝胶过滤色谱法测定。使用实时定量聚合酶链反应（qPCR）测定评价编码CS糖基转移酶的基因的表达。结果：Mankin评分显示病变软骨的退化程度较远侧软骨严重。虽然CS水平在个体之间变化，但病变软骨中的平均CS浓度和链长度分别显著低于远端软骨（浓度：12.04 μ g/mg湿重vs 14.84 μ g/mg湿重，P = 0.021;链长度：5.36 vs 6.19 kDa，P = 0.026）。三个基因编码CS糖基转移酶（CHPF，CSGALNACT 1，CSGALNACT 2）在病变cartilage.Conclusions表达水平较低：在骨关节炎膝关节，CS浓度和链长度减少更接近退化的软骨与降低CS糖基转移酶基因的表达。抑制CS糖基转移酶基因表达可能会减少CS链长度，这可能有助于OA进展。(C)2013年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To determine whether the structure of chondroitin sulfate (CS) in cartilage is reflected by the degree of cartilage degeneration in patients with osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects cartilage degeneration.Design: Two osteoarthritic cartilage samples were obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of 24 knees with end-stage OA. The samples were assigned to two groups as follows: lesion and remote cartilage were adjacent to and remote from the osteoarthritic cartilage, respectively. Histological grade was determined according to the Mankin score. The CS concentration and chain length were determined using high-performance liquid chromatography (HPLC) and gel filtration chromatography, respectively. Expression of the gene encoding CS glycosyltransferase was evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay. These results were compared between lesion and remote cartilage.Results: The Mankin score indicated that lesion cartilage was more degraded compared with remote cartilage. Although the CS levels varied among individuals, the mean CS concentration and chain length were significantly lower and shorter in lesion cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84 p.g/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were expressed at lower levels in lesion cartilage.Conclusions: In the osteoarthritic knee, the CS concentration and chain length were reduced closer to the more degraded cartilage with decreasing CS glycosyltransferase gene expression. Inhibition of CS glycosyltransferase gene expression may reduce CS chain length, which may contribute to OA progression. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.