title: Steroid-independent upregulation of matrix metalloproteinase 9 in chronic rhinosinusitis patients with radiographic evidence of osteitis.
abstract: BACKGROUND
  Chronic sinonasal inflammation is associated with tissue remodeling, such as osteitis, which may be a marker of refractory disease; however, the pathophysiology of osteitis in chronic rhinosinusitis (CRS) is insufficiently understood.
  
  
  METHODS
  Ethmoid mucosa and bone samples were obtained from 35 medically refractory CRS patients and 9 control subjects. Quantitative real-time polymerase chain reaction (RT-PCR) was performed separately on bone and mucosa for matrix metalloproteinase 2 and 9 (MMP2, MMP9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1). Osteitis was classified as mild, moderate, or severe by measuring bone thickness of the maxillary, sphenoid, and ethmoid sinuses on multiplanar computed tomography (CT). Patients were classified based on severity of osteitis and compared to controls.
  
  
  RESULTS
  Nine patients demonstrated radiographic evidence of osteitis (mild = 3, moderate/severe = 6). Bone PCR revealed biologically significant upregulation of MMP9 in all patients with CRS, but the magnitude of the upregulation decreased with severity of osteitis. Mucosa PCR showed upregulation of MMP9 in moderate/severe osteitis only. No significant changes were seen in MMP2 or TIMP1 regulation.
  
  
  CONCLUSIONS
  This is the first study to evaluate the role of MMP in the bone and mucosa of patients with sinonasal osteitis. The pattern of expression suggests there may be a time- and tissue-dependent role for MMP9 in the pathophysiology of osteitis. In addition, MMP9 overexpression is seen despite preoperative oral and intranasal steroid use, suggesting that if MMP9 is an important factor in the development of osteitis then steroids may not be the best treatment in prevention of osteitis.
authors: Division of Rhinology and Sinus Surgery, Oregon Sinus Center, Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA.
authors: Kara Y
authors: KY
authors: Detwiller
authors: Timothy L
authors: TL
authors: Smith
authors: Jess C
authors: JC
authors: Mace
authors: Dennis R
authors: DR
authors: Trune
authors: Nathan B
authors: NB
authors: Sautter
mesh_terms: D002908:Chronic Disease; D018450:Disease Progression; D015521:Ethmoid Sinusitis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D012220:Rhinitis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D013256:Steroids / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: D013256:Steroids; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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