Osteoarthritis (OA) is the most prevalent joint disease causing major disability and medical expenditures. Synovitis is a central feature of OA and is primarily driven by macrophages. Synovial macrophages not only drive inflammation but also its resolution, through a coordinated, simultaneous expression of pro- and anti-inflammatory mechanisms that are essential to counteract damage and recover homeostasis. Current OA therapies are largely based on anti-inflammatory principles and therefore block pro-inflammatory mechanisms such as prostaglandin E₂ and Nuclear factor-kappa B signaling pathways. However, such mechanisms are also innately required for mounting a pro-resolving response, and their blockage often results in chronic low-grade inflammation. Following minor injury, macrophages shield the damaged area and drive tissue repair. If the damage is more extensive, macrophages incite inflammation recruiting more macrophages from the bone marrow to maximize tissue repair and ultimately resolve inflammation. However, sustained damage and inflammation often overwhelms pro-resolving mechanisms of synovial macrophages leading to the chronic inflammation and related tissue degeneration observed in OA. Recently, experimental and clinical studies have shown that joint injection with autologous bone marrow mononuclear cells replenishes inflamed joints with macrophage and hematopoietic progenitors, enhancing mechanisms of inflammation resolution, providing remarkable and long-lasting effects. Besides creating an ideal environment for resolution with high concentrations of interleukin-10 and anabolic growth factors, macrophage progenitors also have a direct role in tissue repair. Macrophages constitute a large part of the early granulation tissue, and further transdifferentiate from myeloid into a mesenchymal phenotype. These cells, characterized as fibrocytes, are essential for repairing osteochondral defects. Ongoing "omics" studies focused on identifying key drivers of macrophage-mediated resolution of joint inflammation and those required for efficient osteochondral repair, have the potential to uncover ways for developing engineered macrophages or off-the-shelf pro-resolving therapies that can benefit patients suffering from many types of arthropaties, not only OA.

中文翻译：

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用于联合治疗的骨髓单核细胞：巨噬细胞在炎症消退和组织修复中的作用。

骨关节炎 (OA) 是最普遍的关节疾病，会导致严重的残疾和医疗支出。滑膜炎是 OA 的一个核心特征，主要由巨噬细胞驱动。滑膜巨噬细胞不仅可以驱动炎症，还可以通过促炎和抗炎机制的协调、同时表达来驱动炎症，这些机制对于抵消损伤和恢复体内平衡至关重要。目前的 OA 疗法主要基于抗炎原理，因此阻断了促炎机制，如前列腺素 E ₂和核因子-κB 信号通路。然而，这些机制也是产生促消退反应的先天必需的，它们的阻塞通常会导致慢性低度炎症。轻伤后，巨噬细胞保护受损区域并驱动组织修复。如果损伤更广泛，巨噬细胞会引发炎症，从骨髓中招募更多的巨噬细胞，以最大限度地修复组织并最终解决炎症。然而，持续的损伤和炎症通常会压倒滑膜巨噬细胞的促消退机制，导致在 OA 中观察到的慢性炎症和相关组织变性。最近，实验和临床研究表明，关节注射自体骨髓单个核细胞可以为发炎的关节补充巨噬细胞和造血祖细胞，增强炎症消退机制，提供显着和持久的效果。除了用高浓度的白细胞介素 10 和合成代谢生长因子为分辨率创造理想的环境外，巨噬细胞祖细胞在组织修复中也有直接作用。巨噬细胞构成了早期肉芽组织的很大一部分，并进一步从髓细胞转分化为间充质表型。这些以纤维细胞为特征的细胞对于修复骨软骨缺损至关重要。正在进行的“组学”研究侧重于确定巨噬细胞介导的关节炎症解决的关键驱动因素以及有效骨软骨修复所需的因素，