Pelassa Simone, Raggi Federica, Prigione Ignazia, Ridella Francesca, Ravelli Angelo, Gattorno Marco, Consolaro Alessandro, Bosco Maria Carla
UOC Rheumatology and Autoinflammatory Diseases, Department of Pediatric Sciences, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal Infantile Sciences (DiNOGMI), University of Genova, Genova, Italy.
Rheumatology (Oxford). 2025 Sep 1;64(9):5162-5171. doi: 10.1093/rheumatology/keaf266.
The objectives of this study were to characterize some phenotypic and functional aspects of fibroblast-like synoviocytes isolated from the Synovial Fluid (SF-FLSs) of patients affected by Juvenile Idiopathic Arthritis (JIA) with active disease and to compare SF-FLS characteristics with those reported in the literature for FLSs of the SM (Synovial Membrane) in adult rheumatic patients.
FLSs were isolated from the SF of JIA patients with active disease by therapeutic arthrocentesis. SF-FLS surface marker expression was assessed by cytofluorimetry; proinflammatory cytokine and MMP gene expression was investigated by quantitative RT-PCR (qRT-PCR); and chondrogenic properties were evaluated by staining with Alcian-Blue.
SF-FLSs display a CD45-,CD34-,CD90+,PDPN+ phenotype and exhibit a significant increase in the expression of genes coding for pro-inflammatory cytokines, but not MMPs, when treated with TNF-α, a cytokine present in the joint environment. In addition, SF-FLSs express the chondrogenic genes BMP4 and Aggrecan (AGG) and show the ability to differentiate towards a chondrocyte-like phenotype when cultured in TGF-β-enriched medium.
FLSs from the SF of JIA patients display a phenotype that has pro-inflammatory, rather than tissue-disruptive, activity; this is similar to what is observed in cells from the sublining region of the SM in adult arthritis patients. In addition, they show chondrogenic ability, indicating the potential for SF-FLSs as an in vitro model for chondrocytes.
本研究的目的是对从患有活动性疾病的幼年特发性关节炎（JIA）患者的滑液（SF-FLSs）中分离出的成纤维样滑膜细胞的一些表型和功能方面进行表征，并将SF-FLS的特征与文献中报道的成年风湿性患者滑膜（SM）的FLS的特征进行比较。
通过治疗性关节穿刺从患有活动性疾病的JIA患者的滑液中分离出FLS。通过细胞荧光法评估SF-FLS表面标志物的表达；通过定量逆转录聚合酶链反应（qRT-PCR）研究促炎细胞因子和基质金属蛋白酶基因的表达；并用阿尔辛蓝染色评估软骨生成特性。
SF-FLS表现出CD45-、CD34-、CD90+、PDPN+表型，并且当用关节环境中存在的细胞因子TNF-α处理时，编码促炎细胞因子的基因表达显著增加，但基质金属蛋白酶的表达没有增加。此外，SF-FLS表达软骨生成基因BMP4和聚集蛋白聚糖（AGG），并且当在富含TGF-β的培养基中培养时显示出向软骨细胞样表型分化的能力。
JIA患者滑液中的FLS表现出具有促炎而非组织破坏活性的表型；这与成年关节炎患者滑膜衬里区域细胞中观察到的情况相似。此外，它们显示出软骨生成能力，表明SF-FLS作为软骨细胞体外模型的潜力。
