Steroid-independent upregulation of matrix metalloproteinase 9 in chronic rhinosinusitis patients with radiographic evidence of osteitis

Kara Y. Detwiller, Timothy Smith, Jess C. Mace, Dennis Trune, Nathan Sautter

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalInternational Forum of Allergy and Rhinology
Volume3
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Osteitis
Matrix Metalloproteinase 9
Up-Regulation
Steroids
Mucous Membrane
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Bone and Bones
Ethmoid Bone
Ethmoid Sinus
Sphenoid Sinus
Polymerase Chain Reaction
Bone Matrix
Maxillary Sinus
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Real-Time Polymerase Chain Reaction
Tomography

Keywords

  • Chronic rhinosinusitis
  • Computed tomography
  • Matrix metalloproteinases
  • MMP9
  • Osteitis
  • Steroids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

Cite this

Steroid-independent upregulation of matrix metalloproteinase 9 in chronic rhinosinusitis patients with radiographic evidence of osteitis. / Detwiller, Kara Y.; Smith, Timothy; Mace, Jess C.; Trune, Dennis; Sautter, Nathan.

In: International Forum of Allergy and Rhinology, Vol. 3, No. 5, 05.2013, p. 364-368.

Research output: Contribution to journalArticle

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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. Conclusion: 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.",
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