The Center for Musculoskeletal Research, University of Rochester, Medical Center 601 Elmwood Avenue, PO Box 665, Rochester, New York, USA.
J Orthop Res. 2011 Sep;29(9):1367-74. doi: 10.1002/jor.21370. Epub 2011 Mar 28.
While bone marrow edema (BME) is diagnostic of spondyloarthropathy, its nature remains poorly understood. In contrast, BME in ankylosing spondylitis is caused by tumor necrosis factor (TNF)-induced vascular and cellular changes. To investigate the relationship between chronic compression and TNF signaling in compression-induced BME we utilized a tail vertebrae compression model with WT, TNF-Tg, and TNFR1&2-/- mice to evaluate: (i) healing following release of chronic compression, (ii) induction of BME in the absence of TNFR, and (iii) efficacy of anti-TNF therapy. Compression-induced normalized marrow contrast enhancement (NMCE) in WT was significantly decreased threefold (p < 0.01) within 2 weeks of release, while the NMCE values in TNF-Tg vertebrae remained elevated, but had a significant decrease (p < 0.05) by 6 weeks after the release of compression. TNFR1&2-/- mice were resistant to compression-induced BME. Anti-TNF therapy did not affect NMCE versus placebo. Histological examination revealed that NMCE values significantly correlated with marrow vascularity and cellularity (p < 0.05), which account for 76% of the variability of NMCE. Collectively, these data demonstrate a critical role for TNF in the induction of chronic compression-induced BME, but not in its maintenance. Amelioration of BME is achieved through biomechanical stability, but is not affected by anti-TNF therapy.
虽然骨髓水肿（BME）是脊柱关节病的诊断特征，但它的性质仍不清楚。相比之下，强直性脊柱炎中的 BME 是由肿瘤坏死因子（TNF）诱导的血管和细胞变化引起的。为了研究慢性压迫与 TNF 信号在压迫诱导的 BME 中的关系，我们利用 WT、TNF-Tg 和 TNFR1&2-/-小鼠的尾椎压迫模型来评估：（i）慢性压迫解除后的愈合情况，（ii）在缺乏 TNFR 的情况下 BME 的诱导，以及（iii）抗 TNF 治疗的效果。WT 小鼠压迫诱导的骨髓对比增强（NMCE）在释放后 2 周内显著降低了三倍（p<0.01），而 TNF-Tg 椎体中的 NMCE 值仍然升高，但在释放压迫后 6 周时显著降低（p<0.05）。TNFR1&2-/-小鼠对压迫诱导的 BME 有抗性。抗 TNF 治疗与安慰剂相比，对 NMCE 没有影响。组织学检查显示，NMCE 值与骨髓血管生成和细胞密度显著相关（p<0.05），这占 NMCE 变异性的 76%。总的来说，这些数据表明 TNF 在慢性压迫诱导的 BME 的诱导中起着关键作用，但在其维持中不起作用。BME 的改善是通过生物力学稳定性实现的，但不受抗 TNF 治疗的影响。
