title: 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.
abstract: 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.
authors: The Center for Musculoskeletal Research, University of Rochester, Medical Center 601 Elmwood Avenue, PO Box 665, Rochester, New York, USA.
authors: M Owen
authors: MO
authors: Papuga
authors: Edmund
authors: E
authors: Kwok
authors: Zhigang
authors: Z
authors: You
authors: Paul T
authors: PT
authors: Rubery
authors: Paul E
authors: PE
authors: Dougherty
authors: Gloria
authors: G
authors: Pryhuber
authors: Christopher A
authors: CA
authors: Beck
authors: Matthew J
authors: MJ
authors: Hilton
authors: Hani A
authors: HA
authors: Awad
authors: Edward M
authors: EM
authors: Schwarz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism* / Q000473:pathology; D005260:Female; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020127:Recovery of Function; D013131:Spine / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013314:Stress, Mechanical; D013623:Tail; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha