Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Tissue Engineering Laboratory, Berlin-Brandenburg Center for Regenerative Therapies and Department of Rheumatology and Clinical Immunology, 10117 Berlin, Germany.
Int J Mol Sci. 2018 Dec 23;20(1):52. doi: 10.3390/ijms20010052.
Thymus-expressed chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), () real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and expression and induced the expression of matrix () , , (), and (). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches.
胸腺表达趋化因子 (CCL25) 是间充质基质细胞的有效细胞趋化因子，因此它是一种候选物，可用于专注于招募内源性修复细胞的原位软骨修复方法。然而，CCL25 对软骨的影响尚不清楚。因此，在这项研究中，我们研究了 CCL25 对组织工程化的健康和骨关节炎软骨的影响。猪软骨细胞在三维 (3D) 微团培养模型中培养，该模型已被证明可模拟人类软骨的关键方面，并且在受到肿瘤坏死因子-α (TNF-α) 刺激时会发生骨关节炎改变。微团培养物单独或与 0.6 nmol/L TNF-α 一起用 CCL25 (0、0.05、0.5、5、50、500 nmol/L) 刺激七天。通过死活染色、番红 O 染色、糖胺聚糖 (GAG) 的组织形态计量学分析、实时 RT-PCR 和猪基因组芯片分析评估效果。500 nmol/L CCL25 导致 GAG 和 表达显著减少，并诱导基质 () 、 、 () 、 和 () 的表达。在低于 500 nmol/L 的浓度下，CCL25 似乎是原位软骨修复治疗方法的候选物。
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