Tsuchida Anika I, Beekhuizen Michiel, 't Hart Marieke C, Radstake Timothy R D J, Dhert Wouter J A, Saris Daniel B F, van Osch Gerjo J V M, Creemers Laura B
Arthritis Res Ther. 2014 Sep 26;16(5):441. doi: 10.1186/s13075-014-0441-0.
This study aimed to evaluate whether profiles of several soluble mediators in synovial fluid and cartilage tissue are pathology-dependent and how their production is related to in vitro tissue formation by chondrocytes from diseased and healthy tissue.
Samples were obtained from donors without joint pathology (n = 39), with focal defects (n = 65) and osteoarthritis (n = 61). A multiplex bead assay (Luminex) was performed measuring up to 21 cytokines: Interleukin (IL)-1α, IL-1β, IL-1RA, IL-4, IL-6, IL-6Rα, IL-7, IL-8, IL-10, IL-13, tumor necrosis factor (TNF)α, Interferon (IFN)γ, oncostatin M (OSM), leukemia inhibitory factor (LIF), adiponectin, leptin, monocyte chemotactic factor (MCP)1, RANTES, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), vascular growth factor (VEGF).
In synovial fluid of patients with cartilage pathology, IL-6, IL-13, IFNγ and OSM levels were higher than in donors without joint pathology (P ≤ 0.001). IL-13, IFNγ and OSM were also different between donors with cartilage defects and OA (P < 0.05). In cartilage tissue from debrided defects, VEGF was higher than in non-pathological or osteoarthritic joints (P ≤ 0.001). IL-1α, IL-6, TNFα and OSM concentrations (in ng/ml) were markedly higher in cartilage tissue than in synovial fluid (P <0.01). Culture of chondrocytes generally led to a massive induction of most cytokines (P < 0.001). Although the release of inflammatory cytokines was also here dependent on the pathological condition (P < 0.001) the actual profiles were different from tissue or synovial fluid and between non-expanded and expanded chondrocytes. Cartilage formation was lower by healthy unexpanded chondrocytes than by osteoarthritic or defect chondrocytes.
Several pro-inflammatory, pro-angiogenic and pro-repair cytokines were elevated in joints with symptomatic cartilage defects and/or osteoarthritis, although different cytokines were elevated in synovial fluid compared to tissue or cells. Hence a clear molecular profile was evident dependent on disease status of the joint, which however changed in composition depending on the biological sample analysed. These alterations did not affect in vitro tissue formation with these chondrocytes, as this was at least as effective or even better compared to healthy chondrocytes.
本研究旨在评估滑液和软骨组织中几种可溶性介质的概况是否与病理状况相关，以及它们的产生与来自患病和健康组织的软骨细胞的体外组织形成有何关系。
样本取自无关节病变的供体（n = 39）、有局灶性缺损的供体（n = 65）和骨关节炎患者（n = 61）。采用多重微珠检测法（Luminex）检测多达21种细胞因子：白细胞介素（IL）-1α、IL-1β、IL-1受体拮抗剂（IL-1RA）、IL-4、IL-6、IL-6受体α（IL-6Rα）、IL-7、IL-8、IL-10、IL-13、肿瘤坏死因子（TNF）α、干扰素（IFN）γ、制瘤素M（OSM）、白血病抑制因子（LIF）、脂联素、瘦素、单核细胞趋化因子（MCP）1、调节激活正常T细胞表达和分泌因子（RANTES）、碱性成纤维细胞生长因子（bFGF）、肝细胞生长因子（HGF）、血管生长因子（VEGF）。
在有软骨病变患者的滑液中，IL-6、IL-13、IFNγ和OSM水平高于无关节病变的供体（P≤0.001）。IL-13、IFNγ和OSM在有软骨缺损的供体与骨关节炎患者之间也存在差异（P<0.05）。在清创缺损的软骨组织中，VEGF高于非病理或骨关节炎关节（P≤0.001）。软骨组织中IL-1α、IL-6、TNFα和OSM的浓度（以ng/ml计）明显高于滑液（P<0.01）。软骨细胞培养通常会导致大多数细胞因子的大量诱导（P<0.001）。虽然炎症细胞因子的释放也取决于病理状况（P<0.001），但其实际概况与组织或滑液不同，且在未扩增和扩增的软骨细胞之间也不同。健康未扩增的软骨细胞形成的软骨比骨关节炎或缺损软骨细胞形成的软骨少。
在有症状性软骨缺损和/或骨关节炎的关节中，几种促炎、促血管生成和促修复的细胞因子升高，尽管与组织或细胞相比，滑液中升高的细胞因子不同。因此，根据关节疾病状态明显有一个清晰的分子概况，然而其组成会根据所分析的生物样本而改变。这些改变并不影响这些软骨细胞的体外组织形成，因为与健康软骨细胞相比，这至少同样有效甚至更好。
