Baboolal Thomas G, Boxall Sally A, Churchman Sarah M, Buckley Conor T, Jones Elena, McGonagle Dennis
Arthritis Res Ther. 2014 Jun 3;16(3):R119. doi: 10.1186/ar4574.
Gelatinous Heberden's nodes (HNs), also termed synovial cysts, are a common form of generalized osteoarthritis (OA). We sought to determine whether HN cases at clinical presentation contained multipotential stromal cells (MSCs) and to explore whether such cells were more closely related to bone marrow (BM) or synovial fluid (SF) MSCs by transcriptional analysis.
At clinical presentation, gelatinous material was extracted/extruded from the distal phalangeal joint of OA patients with HNs. From this, plastic adherent cells were culture-expanded for phenotypic and functional characterization and comparison with BM- and SF-MSCs. Mesenchymal related gene expression was studied by using a custom-designed TaqMan Low Density Array to determine transcriptional similarities between different MSC groups and skin fibroblasts.
In all cases, HN material produced MSC-like colonies. Adherent cultures displayed an MSC phenotype (CD29(+), CD44(+), CD73(+), CD81(+), and CD90(+) and CD14(-) CD19(-), CD31(-), CD34(-), CD45(-), and HLADR(-)) and exhibited osteogenic, chondrogenic lineage differentiation but weak adipogenesis. Gene cluster analysis showed that HN-MSCs were more closely related to SF- than normal or OA BM-MSCs with significantly higher expression of synovium-related gene markers such as bone morphogenic protein 4 (BMP4), bone morphogenetic protein receptor type 1A (BMPR1A), protein/leucine-rich end leucine-rich repeat protein (PRELP), secreted frizzled-related protein 4 (SFRP4), and tumor necrosis factor alpha-induced protein 6 (TNFAIP6) (P <0.05).
Gelatinous HNs derived from hand OA at clinical presentation contain a population of MSCs that share transcriptional similarities with SF-derived MSCs. Their aberrant entrapment within the synovial cysts may impact on their normal role in joint homeostasis.
胶冻样赫伯登结节(HNs),也称为滑膜囊肿,是全身性骨关节炎(OA)的一种常见形式。我们试图确定临床表现为HN的病例中是否含有多能间充质干细胞(MSCs),并通过转录分析探讨这些细胞与骨髓(BM)或滑膜液(SF)来源的MSCs是否关系更为密切。
在临床表现时,从患有HNs的OA患者的远端指间关节中提取/挤出胶冻样物质。从中培养扩增塑料贴壁细胞,进行表型和功能鉴定,并与BM-MSCs和SF-MSCs进行比较。使用定制设计的TaqMan低密度阵列研究间充质相关基因表达,以确定不同MSC组与皮肤成纤维细胞之间的转录相似性。
在所有病例中,HN物质均产生了类似MSC的集落。贴壁培养物表现出MSC表型(CD29(+)、CD44(+)、CD73(+)、CD81(+)、CD90(+)以及CD14(-)、CD19(-)、CD31(-)、CD34(-)、CD45(-)和HLADR(-)),并表现出成骨、软骨形成谱系分化,但脂肪生成较弱。基因聚类分析表明,HN-MSCs与SF-MSCs的关系比正常或OA BM-MSCs更为密切,骨形态发生蛋白4(BMP4)、骨形态发生蛋白1A型受体(BMPR1A)、富含脯氨酸/亮氨酸的末端富含亮氨酸重复蛋白(PRELP)、分泌型卷曲相关蛋白4(SFRP4)和肿瘤坏死因子α诱导蛋白6(TNFAIP6)等滑膜相关基因标志物的表达显著更高(P<0.05)。
临床表现为手部OA的胶冻样HNs含有一群与SF来源的MSCs具有转录相似性的MSCs。它们在滑膜囊肿内的异常滞留可能会影响其在关节稳态中的正常作用。