The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for “drivers” of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

慢性非细菌性骨髓炎（CNO）的病理生理学仍不完全了解。提示CNO患者单核细胞中NLRP3炎症小体激活增加和IL-1β释放有助于骨骼炎症。在这里，我们解剖免疫细胞浸润，并证明了跨疾病阶段的单核细胞的参与。细胞密度和免疫细胞组成的差异可能有助于区分BOM和CNO。但是，差异是微妙的，CNO的浸润度也不同。与涉及的其他细胞相比，单核细胞在CNO的所有阶段都是稳定的元素，这使其成为寻找炎症“驱动器”的有希望的候选者。此外，我们将单核细胞中炎性体成分NLRP3和ASC的表达增加与相应基因周围的位点特异性DNA低甲基化联系起来NLRP3和PYCARD。我们的观察结果为促炎性单核细胞参与CNO的病理生理提供了进一步的证据。细胞和分子改变可以用作疾病生物标志物和/或治疗靶标。