TNF is required for the induction but not the maintenance of compression-induced BME signals in murine tail vertebrae: limitations of anti-TNF therapy for degenerative disc disease.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Papuga, MO; Kwok, E; You, Z; Rubery, PT; Dougherty, PE; Pryhuber, G; Beck, CA; Hilton, MJ; Awad, HA; Schwarz, EM

Published Date

  • September 2011

Published In

Volume / Issue

  • 29 / 9

Start / End Page

  • 1367 - 1374

PubMed ID

  • 21445993

Electronic International Standard Serial Number (EISSN)

  • 1554-527X

International Standard Serial Number (ISSN)

  • 0736-0266

Digital Object Identifier (DOI)

  • 10.1002/jor.21370

Language

  • eng