title: Dose-dependent expression of neuronal injury markers during experimental osteoarthritis induced by monoiodoacetate in the rat.
abstract: BACKGROUND
  It was recently reported that the mono-iodoacetate (MIA) experimental model of osteoarthritis (OA) courses with changes of neurons innervating the affected joints that are commonly interpreted as a neuronal response to axonal injury. To better characterize these changes, we evaluated the expression of two markers of neuronal damage, ATF-3 and NPY, and the growth associated protein GAP-43, in primary afferent neurons of OA animals injected with three different doses of MIA (0.3, 1 or 2 mg). Measurements were performed at days 3, 7, 14, 21 and 31 post-MIA injection.
  
  
  RESULTS
  OA animals showed the characteristic histopathological changes of the joints and the accompanying nociceptive behaviour, evaluated by the Knee-Bed and CatWalk tests. An increase of ATF-3 expression was detected in the DRG of OA animals as early as 3 days after the injection of 1 or 2 mg of MIA and 7 days after the injection of 0.3 mg. NPY expression was increased in animals injected with 1 or 2 mg of MIA, at day 3 or in all time-points, respectively. From day 7 onwards there was a massive increase of GAP-43 expression in ATF-3 cells.
  
  
  CONCLUSIONS
  The expression of the neuronal injury markers ATF-3 and NPY as well as an up-regulation of GAP-43 expression, indicative of peripheral fibre regeneration, suggests that axonal injury and a regeneration response may be happening in this model of OA. This opens new perspectives in the unravelling of the physiopathology of the human disease.
authors: Department of Experimental Biology, University of Porto, Alameda Prof. Hernani Monteiro, Porto, 4200-319, Portugal. jogomes@med.up.pt
authors: Joana
authors: J
authors: Ferreira-Gomes
authors: Sara
authors: S
authors: Adães
authors: Raquel Meireles
authors: RM
authors: Sousa
authors: Marcelo
authors: M
authors: Mendonça
authors: José Manuel
authors: JM
authors: Castro-Lopes
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019807:Iodoacetic Acid; D007719:Knee Joint / Q000294:innervation / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009478:Neuropeptide Y / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D015415:Biomarkers; D019922:GAP-43 Protein; D009478:Neuropeptide Y; D019807:Iodoacetic Acid