医学
促炎细胞因子
骨关节炎
软骨
关节软骨损伤
软骨细胞
白细胞介素
细胞外基质
基质金属蛋白酶
病理
滑液
免疫学
关节软骨
炎症
细胞因子
解剖
内科学
细胞生物学
生物
替代医学
作者
Nicholas Allen,Bijan Abar,Richard Danilkowicz,Virginia B. Kraus,Steven A. Olson,Samuel B. Adams
标识
DOI:10.1177/10711007211046952
摘要
Intra-articular ankle fracture (IAF) causes posttraumatic osteoarthritis (PTOA), but the exact mechanism is unknown. Proinflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH) but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents.Synovial fluid was obtained from 54 IAFs and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control-media only, (B) SFFH from days 0 to 2 after fracture, (C) SFFH from days 3 to 9, (D) SFFH from days 10 to 14, (E) group B + interleukin 1 receptor antagonist (IL-1Ra), and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators.Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloproteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups.Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response.IAFs create an adverse intra-articular environment consisting of significantly increased levels of inflammatory cytokines and MMPs able to damage cartilage throughout the joint. These data suggest that the acute addition of specific inflammatory inhibitors may decrease the levels of these proinflammatory mediators.
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