Molecular Characterization of Articular Cartilage from Young Adults with Femoroacetabular Impingement
Molecular Characterization of Articular Cartilage from Young Adults with Femoroacetabular Impingement
复制标题
股骨髋臼撞击年轻人关节软骨的分子特征。
DOI：
10.2106/jbjs.l.00497
复制
发表时间：
2013-08-21
影响因子：
5.3
通讯作者：
Clohisy, John C.
中科院分区：
文献类型：
--
作者：
Hashimoto, Shingo;Rai, Muhammad Farooq;Clohisy, John C.
背景
股骨髋臼撞击是髋关节疼痛的常见原因，并可能导致继发性骨关节炎，但对机械性髋关节撞击和关节软骨退变之间的分子事件知之甚少。本研究的第一个目标是量化从对照髋关节和股骨髋臼撞击和终末期骨关节炎髋关节采集的关节软骨中炎性细胞因子和趋化因子、基质降解和细胞外基质基因的表达。第二个目标是分析这些基因在骨关节炎不同阶段关节软骨中的相对表达。
方法
从因股骨髋臼撞击或髋关节成形术而接受髋关节保留手术的32个髋关节中获得了肱骨样本。还分析了三个对照软骨样品。术中根据软骨损伤的严重程度对标本进行分级，记录放射学骨关节炎分级，并进行定量RT-PCR（实时聚合酶链反应）以确定相关基因表达。
结果
除IL-1 β和CXCL 2外，所有其他趋化因子的（信使RNA）表达（IL-8、CXCL 1、CXCL 3、CXCL 6、CCL 3和CCL 3L 1），基质降解（基质金属蛋白酶[MMP]-13和ADAMTS-4），和结构基质与骨关节炎髋关节和正常对照相比，股骨髋臼撞击髋关节软骨中的COL 2A 1 [胶原蛋白，II型，α]和ACAN [聚集蛋白]基因总体较高。这10个定量基因中有7个的差异达到显著性（p ≤ 0.05），与对照组相比，股骨髋臼撞击组的CXCL 3、CXCL 6和COL 2A 1升高，与骨关节炎和对照组相比，IL-8、CCL 3L 1、ADAMTS-4和ACAN升高。当根据退行性级联反应的阶段对样本进行分组时，在股骨髋臼撞击的两个中间阶段（软骨软化或分裂/变薄）之一中，mRNA表达相对较高，IL-8、CXCL 2、CXCL 3、CCL 3L 1和ACAN的差异达到显著性。与股骨髋臼撞击相比，ACAN表达在骨关节炎髋关节中减少，但与对照关节软骨相比升高。
结论
来自股骨髋臼撞击的髋关节撞击区的关节软骨（特别是那些处于卵裂/变薄阶段的髋关节）表达了更高水平的某些炎症、合成代谢和分解代谢基因，代表了更高的代谢状态。
临床相关性
股骨髋臼撞击的髋关节撞击区的关节软骨代谢过度活跃，支持这种撞击是髋关节骨关节炎的结构前兆的概念。
BACKGROUND
Femoroacetabular impingement is a frequent cause of hip pain and may lead to secondary osteoarthritis, yet little is known about the molecular events linking mechanical hip impingement and articular cartilage degeneration. The first goal of this study was to quantify the expression of inflammatory cytokine and chemokine, matrix-degrading, and extracellular matrix genes in articular cartilage harvested from control hips and hips with femoroacetabular impingement and end-stage osteoarthritis. The second goal was to analyze the relative expression of these genes in articular cartilage harvested at various stages of osteoarthritis.
METHODS
Cartilage samples were obtained from thirty-two hips undergoing hip preservation surgery for femoroacetabular impingement or hip arthroplasty. Three control cartilage samples were also analyzed. Specimens were graded intraoperatively with regard to the severity of cartilage damage, the radiographic osteoarthritis grade was recorded, and quantitative RT-PCR (real-time polymerase chain reaction) was performed to determine relative gene expression.
RESULTS
Except for interleukin-1β (IL-1β) and CXCL2, the mRNA (messenger RNA) expression of all other chemokine (IL-8, CXCL1, CXCL3, CXCL6, CCL3, and CCL3L1), matrix-degrading (matrix metalloproteinase [MMP]-13 and ADAMTS-4), and structural matrix (COL2A1 [collagen, type II, alpha] and ACAN [aggregan]) genes was higher overall in cartilage from hips with femoroacetabular impingement compared with hips with osteoarthritis and normal controls. The differences reached significance (p ≤ 0.05) for seven of these ten quantified genes, with CXCL3, CXCL6, and COL2A1 being elevated in the femoroacetabular impingement group compared with only the control group and IL-8, CCL3L1, ADAMTS-4, and ACAN being elevated compared with both the osteoarthritis and control groups. When samples were grouped according to the stage of the degenerative cascade, mRNA expression was relatively higher in one of the two middle stages of femoroacetabular impingement (chondromalacia or cleavage/thinning), with the difference reaching significance for IL-8, CXCL2, CXCL3, CCL3L1, and ACAN. ACAN expression was diminished in hips with osteoarthritis compared with femoroacetabular impingement but elevated compared with the control articular cartilage.
CONCLUSIONS
Articular cartilage from the impingement zone of hips with femoroacetabular impingement (and particularly those hips in the cleavage/thinning stage) expressed higher levels of certain inflammatory, anabolic, and catabolic genes, representing a heightened metabolic state.
CLINICAL RELEVANCE
The articular cartilage from the impingement zone of hips with femoroacetabular impingement was metabolically hyperactive, supporting the concept that such impingement is a structural precursor to hip osteoarthritis.