Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.

中文翻译：

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骨髓源性抑制细胞的扩增通过软骨下骨重塑促进代谢性骨关节炎

急性关节损伤后的骨关节炎 (OA) 占所有关节病的很大一部分。骨髓源性抑制细胞 (MDSCs) 是一种异质性骨髓祖细胞群，通常以有效的免疫抑制活性而闻名；然而，MDSCs 也可以分化为破骨细胞。此外，已知该人群在代谢疾病期间会扩大。本研究的目的是确定 MDSCs 在 OA 病理生理学背景下的作用。在这项研究中，我们使用 OA 小鼠模型和 MDSC 定量研究了 MDSCs 在体外和体内成为破骨细胞的分化和功能能力，以及与肥胖状态相关的 OA 病理学人类的 MDSC 定量。我们观察到 MDSCs 在肥胖期间在小鼠和人类中扩增。与喂食低脂饮食 (LFD) 的小鼠相比，相对于体重指数和喂食高脂饮食 (HFD) 的小鼠，MDSC 在 OA 受试者的外周血中扩增。在小鼠中，单核细胞 MDSC (M-MDSC) 在饮食诱导的肥胖 (DIO) 中扩大，在内侧半月板 (DMM) 手术不稳定后进一步扩大以诱导创伤后 OA (PTOA)（与假手术对照相比） ）。来自 DIO 小鼠的 M-MDSCs 在培养物中形成破骨细胞的能力更强，软骨下骨破骨细胞数量增加。在人类中，与患有 OA 的瘦受试者相比，我们观察到肥胖受试者外周血和滑液中 M-MDSC 的扩增。这些数据表明 MDSCs 在代谢疾病中被重新编程，有可能促进 OA 的进展和严重程度。