Identification of parotid salivary biomarkers in Sjögren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis

Ryu, Ok Hee; Atkinson, Jane C.; Hoehn, Gerard; Illei, G.; Hart, Thomas C.

doi:10.1093/rheumatology/kei212

Cited by 191 publications

(158 citation statements)

References 49 publications

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“…The database search process, excluded and included articles, as well as reasons for the exclusion are shown in Figure 1. Twenty-one articles were selected for full text review and abstracted, with information (disease, sample size, saliva type collected, selection of controls, analytical method utilized, and biomarkers identified) documented in Tables 1 and 2 and Supplementary Table 1 (Dowling et al, 2008;Fleissig et al, 2009;Giusti et al, 2007aGiusti et al, , 2007bHirtz et al, 2006;Hu et al, 2007bHu et al, , 2007cHu et al, , 2008Huang, 2004;Imanguli et al, 2007;Ohsiro et al, 2007;Peluso et al, 2007;Preza et al, 2009;Rao et al, 2009;Ryu et al, 2006;Streckfus et al, 2006Streckfus et al, , 2008Vitorino et al, 2006;Wu et al, 2009aWu et al, , 2009bYang et al, 2006). This systematic review is the first to evaluate the MSbased proteomic studies that utilized saliva to define biomarkers related to specific diseases.…”

Section: Resultsmentioning

confidence: 99%

Defining Salivary Biomarkers Using Mass Spectrometry-Based Proteomics: A Systematic Review

AlTarawneh

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Dibble

et al. 2011

OMICS: A Journal of Integrative Biology

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Recent advancements in mass spectrometric proteomics provide a promising result in utilizing saliva to explore biomarkers for diagnostic purposes. However, the issues of specificity or redundancy of disease-associated salivary biomarkers have not been described. This systematic review was therefore aimed to define and summarize disease-related salivary biomarkers identified by mass spectrometry proteomics. Peer-reviewed articles published through July 2009 within three databases were reviewed. Out of 243 articles, 21 studies were selected in this systematic review with conditions including Sjö gren's syndrome, squamous cell carcinoma, dental caries, diabetes, breast cancer, periodontitis, gastric cancer, systemic sclerosis, oral lichen planus, bleeding oral cavity, and graft-versus-host disease. The sample size ranged from 3-41 in both diseased and control subjects, with no consensus on sample collection protocol. One hundred eighty biomarkers were identified in total; 87 upregulated, 63 downregulated, and 30 varying based on disease. Except for Sjö gren's syndrome, the majority of studies with the same disease produce inconsistent biomarkers. Larger sample size and standardization of sample collection/treatment protocol may improve future studies.

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Section: Resultsmentioning

confidence: 99%

Defining Salivary Biomarkers Using Mass Spectrometry-Based Proteomics: A Systematic Review

AlTarawneh

Border

Dibble

et al. 2011

OMICS: A Journal of Integrative Biology

158

130

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“…In the 9 patients with secondary SS, 18 of the 62 salivary proteins analyzed (29%) were identifiable in a significantly lower percentage of secondary SS patients than in the controls, 2 (IB-1 and statherin) showed significantly lower levels than in the controls, and 3 (IB-6, P-B Des [1][2][3][4] , and ␤-defensin 2) were identifiable in a significantly higher percentage of secondary SS patients than in the controls.…”

Section: Frequencies and Levels Of Salivary Gland Proteins In Primarymentioning

confidence: 90%

“…The composition of saliva in patients with primary SS has been found to be different from that in normal subjects (4). However, the pattern of salivary gland proteins in primary SS patients has not yet been completely defined with regard to its composition, mainly in relation to low molecular weight components, such as acidic and basic proline-rich proteins (PRPs), statherins, histatins, and cystatins, as well as defensins, which are immunopeptides of epithelial and neutrophilic origin.…”

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confidence: 99%

Proteomic study of salivary peptides and proteins in patients with Sjögren's syndrome before and after pilocarpine treatment

Peluso¹,

Santis²,

Inzitari³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate the effect of pilocarpine on the salivary peptide and protein profile in patients with primary Sjögren's syndrome (SS) and to study the differences between patients with primary SS, patients with SS associated with other rheumatic diseases, and healthy control subjects.Methods. Saliva specimens were obtained from 9 primary SS patients, 9 secondary SS patients, and 10 healthy controls. Samples were analyzed for levels of 62 different salivary proteins using high-performance liquid chromatography coupled with mass spectrometry using a spectrometer equipped with an electrospray ionization source. In 6 of the primary SS patients, saliva was collected at 30 minutes, 60 minutes, and 24 hours after taking 5 mg of pilocarpine.Results. Before pilocarpine, ϳ60% of salivary proteins in samples from primary SS patients were not identifiable or showed lower levels than those in healthy controls. After 30-60 minutes following pilocarpine treatment, approximately one-third of the less represented proteins was found in a similar percentage of primary SS patients and controls. Almost all of the proteins that were detectable at lower levels in primary SS patients compared with controls reached levels similar to those in controls at 30-60 minutes after pilocarpine. The parotid gland proteins had the best response to pilocarpine. Primary SS patients were characterized by higher ␣-defensin 1 levels and by the presence of ␤-defensin 2. Secondary SS patients showed an intermediate protein profile between that of the primary SS patients and the controls. Conclusion. Pilocarpine partially restored the levels and numbers of identifiable proteins in saliva from patients with primary SS. Higher levels of ␣-defensin 1 and the presence of ␤-defensin 2 in the saliva of patients with primary SS could be markers of oral inflammation in this patient group.Saliva is a complex fluid composed of a variety of electrolytes, metabolites, nucleotides, polynucleotides, and proteins. This fluid plays an important role in the maintenance of oral health. The rate of salivary protein secretion is controlled mainly by noradrenaline, which is released from the sympathetic terminals and acts through the ␤-adrenergic receptors. The rate of fluid and electrolyte secretion is controlled by acetylcholine, which is released from the parasympathetic terminals and acts through the muscarinic cholinergic receptors.A large number of systemic agents have been proposed as secretagogues, but only a few have shown consistent salivary secretion-enhancing properties in well-designed trials. Among cholinergic agonists, studies in rats have shown that pilocarpine is the most effective for protein secretion (1) and has mild ␤-adrenergic stimulatory properties; however, few data in humans have been reported. Pilocarpine has been shown to improve symptoms of oral dryness and to increase salivary output in patients with primary Sjögren's syndrome (SS) (2), a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates and con...

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“…Mass fingerprint analysis was performed using a MALDI-TOF-MS (Proteomics Analyzer 4700, Applied Biosystems, Foster City, CA) as described previously. [23] Database searches based on Mascot 2.0 (Matrix Science) individual MSMS ion scores were performed against SwissProt. Ion scores >95% CI were considered significant.…”

Section: Two Dimensional-differential In Gel Electrophoresis (2d-digementioning

confidence: 99%

A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro

Choi

Song

Ryu

et al. 2008

Bone

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A 4 base-pair deletion mutation in the Distal-Less 3 (DLX3) gene is etiologic for Tricho-DentoOsseous syndrome (TDO). A cardinal feature of TDO is an increased thickness and density of bone. We tested the effects of the DLX3 gene mutation responsible for TDO on the osteoblastic differentiation of preosteoblastic MC3T3E1 cells and multipontent mesenchymal C2C12 cells. Differential expression analysis of C2C12 cells transfected with wild type DLX3 or mutant DLX3 was performed and desmin gene expression, an early myoblastic differentiation marker in mesenchymal cells, was evaluated by RT-PCR, western blot analysis, and desmin promoter transcriptional activity. Transfection of wild type DLX3 into MC3T3E1 and C2C12 cells increased alkaline phosphatase-2 activity, mineral deposition, and promoter activities of the osteocalcin and type1 collagen genes compared to empty vector transfected cells. Transfection of mutant DLX3 into these cells further enhanced alkaline phosphatase activity, mineral deposition, and osteocalcin promoter activities, but did not further enhance type 1 collagen promoter activity. Transfection of mutant DLX3 into C2C12 cells markedly down regulated desmin gene expression, and protein expression of desmin and MyoD, while increasing protein expression of osterix and Runx2. These results demonstrate that the DLX3 deletion mutation associated with TDO enhances mesenchymal cell differentiation to an osteoblastic lineage rather than a myoblastic lineage by changing the fate of mesenchymal cells. This DLX3 mutation also accelerates the differentiation of osteoprogenitor cells to osteoblasts at later stages of osteogenesis.

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Identification of parotid salivary biomarkers in Sjögren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis

Abstract: The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS.

Cited by 191 publications

References 49 publications

Defining Salivary Biomarkers Using Mass Spectrometry-Based Proteomics: A Systematic Review

Defining Salivary Biomarkers Using Mass Spectrometry-Based Proteomics: A Systematic Review

Proteomic study of salivary peptides and proteins in patients with Sjögren's syndrome before and after pilocarpine treatment

A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro

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