Department of Orthopaedics and Sports Medicine, Erasmus MC, Rotterdam, The Netherlands.
Department of Otorhinolaryngology, Erasmus MC, Rotterdam, The Netherlands.
Cartilage. 2022 Jan-Mar;13(1):19476035221085136. doi: 10.1177/19476035221085136.
Inflammation is known to negatively affect cartilage repair. However, it is unclear how inflammation influences the migration of mesenchymal stromal cells (MSCs) from the underlying bone marrow into the defect. We therefore aimed to investigate how synovial inflammation influences MSC migration, and whether modulation of inflammation with triamcinolone acetonide (TAA) may influence migration.
Inflamed human osteoarthritic synovium, M(IFNγ+TNFα) pro-inflammatory macrophages, M(IL4) repair macrophages, M(IL10) anti-inflammatory macrophages, or synovial fibroblasts were cultured with/without TAA. Conditioned medium (CM) was harvested after 24 hours, and the effect on MSC migration was studied using a Boyden chamber assay. Inflammation was evaluated with gene expression and flow cytometry analysis.
Synovium CM increased MSC migration. Modulation of synovial inflammation with TAA further increased migration 1.5-fold ( < 0.01). TAA significantly decreased , , and gene expression in synovium explants and increased , a gene associated with anti-inflammatory macrophages. TAA treatment decreased the percentage of CD14+/CD80+ and CD14+/CD86+ pro-inflammatory macrophages and increased the percentage of CD14+/CD163+ anti-inflammatory macrophages in synovium explants. Interestingly, MSC migration was specifically enhanced by medium conditioned by M(IL4) macrophages and by M(IL10) macrophages treated with TAA, and unaffected by CM from M(IFNγ+TNFα) macrophages and synovial fibroblasts.
Macrophages secrete factors that stimulate the migration of MSCs. Modulation with TAA increased specifically the ability of anti-inflammatory macrophages to stimulate migration, indicating that they play an important role in secreting factors to attract MSCs. Modulating inflammation and thereby improving migration could be used in approaches based on endogenous repair of full-thickness cartilage defects.
炎症被认为会对软骨修复产生负面影响。然而，炎症如何影响间充质基质细胞（MSCs）从骨髓下方迁移到缺损处尚不清楚。因此，我们旨在研究滑膜炎症如何影响 MSC 的迁移，以及用曲安奈德（TAA）调节炎症是否会影响迁移。
培养炎性人骨关节炎滑膜、M（IFNγ+TNFα）促炎巨噬细胞、M（IL4）修复巨噬细胞、M（IL10）抗炎巨噬细胞或滑膜成纤维细胞，并用/不用 TAA。24 小时后收获条件培养基（CM），并通过 Boyden 室测定法研究其对 MSC 迁移的影响。通过基因表达和流式细胞术分析评估炎症。
滑膜 CM 增加了 MSC 的迁移。用 TAA 调节滑膜炎症进一步使迁移增加了 1.5 倍（<0.01）。TAA 显著降低了滑膜组织中的 、 和 基因表达，并增加了与抗炎巨噬细胞相关的 基因表达。TAA 治疗降低了滑膜组织中 CD14+/CD80+和 CD14+/CD86+促炎巨噬细胞的百分比，增加了 CD14+/CD163+抗炎巨噬细胞的百分比。有趣的是，MSC 迁移仅被 M（IL4）巨噬细胞条件培养基和用 TAA 处理的 M（IL10）巨噬细胞的 CM 特异性增强，而不受 M（IFNγ+TNFα）巨噬细胞和滑膜成纤维细胞 CM 的影响。
巨噬细胞分泌刺激 MSC 迁移的因子。用 TAA 调节增加了抗炎巨噬细胞刺激迁移的能力，表明它们在分泌吸引 MSC 的因子方面发挥着重要作用。调节炎症从而改善迁移可用于基于全层软骨缺损内源性修复的方法。
