title: Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.
abstract: OBJECTIVE
  The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis.
  
  
  METHODS
  Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157).
  
  
  CONCLUSIONS
  Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.
authors.affiliation: Division of Periodontology, University of Minnesota School of Dentistry, Minneapolis, MN, USA.
authors.forename: V
authors.initials: V
authors.lastname: Thumbigere-Math
authors.forename: B S
authors.initials: BS
authors.lastname: Michalowicz
authors.forename: E P
authors.initials: EP
authors.lastname: de Jong
authors.forename: T J
authors.initials: TJ
authors.lastname: Griffin
authors.forename: D L
authors.initials: DL
authors.lastname: Basi
authors.forename: P J
authors.initials: PJ
authors.lastname: Hughes
authors.forename: M L
authors.initials: ML
authors.lastname: Tsai
authors.forename: K K
authors.initials: KK
authors.lastname: Swenson
authors.forename: L
authors.initials: L
authors.lastname: Rockwell
authors.forename: R
authors.initials: R
authors.lastname: Gopalakrishnan
mesh_terms: D015415:Biomarkers / Q000032:analysis; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D051180:Desmoplakins / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D012463:Saliva / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D051180:Desmoplakins; D011506:Proteins; D020780:Matrix Metalloproteinase 9
keywords: biological markers; biomarkers; bisphosphonate; bisphosphonate-related osteonecrosis of the jaw; osteonecrosis of the jaw; proteomics; saliva