Arthritis Rheumatol. 2015 Feb;67(2):435-41. doi: 10.1002/art.38930.
Articular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA–associated changes in human acetabular labrum cells.
Microarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3-dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells.
Pathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor β signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly down-regulated in OA labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells.
OA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.
关节软骨在骨关节炎(OA)中研究得很好。然而,支撑结构(如环绕髋关节的密封结构髋臼唇)的作用研究得要少得多。我们最近表明纤维软骨细胞是代谢活跃的。本研究旨在研究与人类髋臼唇细胞相关的髋 OA 变化。
通过微阵列分析比较在 3 维藻酸盐珠系统中培养的 OA 唇细胞和健康唇细胞。使用基因集富集分析软件对数据进行聚类分析,并使用 PANTHER 基因家族工具对基因列表进行分析。通过对唇和软骨样本的定量聚合酶链反应分析和免疫组织化学验证选择的候选物。通过体外刺激实验在唇细胞中研究鉴定基因的功能影响。
途径分析显示 OA 唇细胞中的细胞因子和趋化因子信号增加,而细胞外基质相互作用和转化生长因子 β 信号减少。与健康唇相比,OA 中几个基因的表达明显不同。我们特别关注 3 种小富含亮氨酸重复蛋白(SLRPs)、骨调节素、骨粘连蛋白和软骨寡聚基质蛋白,它们在 OA 唇中似乎明显受到调节与 OA 软骨。SLRPs 在 OA 唇中强烈下调,但在 OA 关节软骨中上调。此外,体外刺激骨调节素增加了 OA 唇细胞中聚集蛋白的表达。
OA 唇纤维软骨细胞具有与 OA 软骨细胞相似的几个特征。然而,SLRP 的表达似乎受到 OA 唇和软骨退变的不同影响,这表明这种支撑结构在 OA 中具有特定的作用。SLRPs 对唇细胞的功能影响使它们成为髋 OA 进一步研究的有趣目标。