Adams Samuel B, Reilly Rachel M, Huebner Janet L, Kraus Virginia B, Nettles Dana L
1 Duke University Medical Center, Durham, NC, USA.
3 Duke Molecular Physiology Institute, Durham, NC, USA.
Foot Ankle Int. 2017 Oct;38(10):1055-1063. doi: 10.1177/1071100717728234. Epub 2017 Sep 11.
The study objective was to examine the effect of time and fracture severity on the undiluted synovial fluid (SF) microenvironment during the acute phase following intra-articular fracture (IAF) of the human ankle.
Ankle SF from 54 patients with an acute IAF was analyzed for concentrations of 10 cytokines, 5 matrix metalloproteinases, 2 products of cartilage catabolism, and combined products of heme metabolism. All analytes were correlated with time from fracture and further analyzed for an effect of 3 time subgroups (0-2 days, 3-9 days, and ≥10 days) corresponding to timepoints for clinical ankle fracture interventions. The effect of fracture severity was determined by grouping SF according to the number of radiographic intra-articular fracture lines.
Fifteen of 18 analytes were significantly correlated with time. Temporal grouping of SF revealed an initial (0-2 days) spike of pro-inflammatory (IL-12p70, IL-1β, IL-6) and anti-inflammatory (IL-10 and IL-4) cytokines, matrix metalloproteinases (MMP) MMP-9, and sGAG, followed immediately (3-9 days) by products of heme metabolism and an unchallenged surge in mediators and products of cartilage catabolism (MMP-1, MMP-2, MMP-3, MMP-10, and CTX-II). After 10 days, there was a decrease in pro- and anti-inflammatory cytokines but a persistence of mediators of ECM catabolism. There was no clear relationship between the number of fracture lines and SF levels of analytes.
This study demonstrated acute temporal fluctuations following ankle IAF resulting in an overall catabolic environment by 10 days post-fracture and supports consideration of an early evacuation of the joint space to reduce the intra-articular inflammatory burden. Clinical Relavence: This study contributes to the understanding of the intra-articular events that potentially contribute to the development of posttraumatic osteoarthritis acutely following IAF in the ankle.
本研究的目的是探讨时间和骨折严重程度对人踝关节关节内骨折（IAF）急性期未稀释滑液（SF）微环境的影响。
对54例急性IAF患者的踝关节SF进行分析，检测10种细胞因子、5种基质金属蛋白酶、2种软骨分解代谢产物和血红素代谢联合产物的浓度。所有分析物均与骨折后的时间相关，并进一步分析了对应于临床踝关节骨折干预时间点的3个时间亚组（0 - 2天、3 - 9天和≥10天）的影响。根据X线关节内骨折线的数量对SF进行分组，以确定骨折严重程度的影响。
18种分析物中的15种与时间显著相关。SF的时间分组显示，促炎（IL - 12p70、IL - 1β、IL - 6）和抗炎（IL - 10和IL - 4）细胞因子、基质金属蛋白酶（MMP）MMP - 9和糖胺聚糖（sGAG）在最初（0 - 2天）出现峰值，随后立即（3 - 9天）出现血红素代谢产物以及软骨分解代谢介质和产物（MMP - 1、MMP - 2、MMP - 3、MMP - 10和CTX - II）的无挑战激增。10天后，促炎和抗炎细胞因子减少，但细胞外基质分解代谢介质持续存在。骨折线数量与分析物的SF水平之间没有明确的关系。
本研究表明踝关节IAF后存在急性时间波动，导致骨折后10天出现整体分解代谢环境，并支持考虑早期清除关节腔以减轻关节内炎症负担。临床意义：本研究有助于理解踝关节IAF后急性期可能导致创伤后骨关节炎发展的关节内事件。
