To investigate if level of collagenase-2 and collagenase-3 in PISF act as mediators in the process of bone destruction in peri-implantitis
PISF samples
N/A
aMMP-8 by IFMA
13 subjects aged from 23 to 89 years old
Peri-implantitis
Gingival Index is not a clinically important marker for bone loss, but aMMP-8 and MMP-13 in PISF are. They might participate in peri-implant osteolysis
2
Levels and molecular forms of MMP-7 (matrilysin-1) and MMP-8 (collagenase-2) in diseased human peri-implant sulcular fluid [22]
To identify various isoforms of MMP-8 in PISF and its relationship with MMP-7
PISF samples
N/A
aMMP-8 levels were determined by the western immunoblot method with polyclonal anti-human-MMP-8
13 subjects aged from 21 to 86 years old
Peri-implantitis
The elevated levels of aMMP-8 and MMP-7 were identified in active forms in diseased PISF, but MMP-7 was less prominent. MMP inhibitors, potential future tissue protective drugs, seemingly do not interfere with the defensive antibacterial action of MMP-7 but can inhibit aMMP-8
3
Laminin-5 gamma2-chain and collagenase-2 (MMP-8) in human peri-implant sulcular fluid [23]
To investigate the forms and concentration of MMP-8 and laminin-5 gamma2-chain in PISF and to find correlation of these two with clinical parameters (i.e., the recorded gingival and bone resorption) of peri-implantitis
PISF samples
N/A
aMMP-8 levels were determined by western immunoblot
13 subjects aged from 21 to 86 years old
Peri-implantitis
aMMP-8 is a important biomarker of peri-implantitis, but longitudinal studies are required to assess their use, either alone or in combination as molecular biochemical PISF markers, to predict the risk of progression of peri-implantitis, as well as to monitor the impact of treatment of the disease
4
Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis [24]
To develop a test stick for detection of MMP-8 in GCF, to evaluate its diagnostic potential as point-of-care/chair-side test, and to monitor the response to treatment of periodontitis
GCF samples
N/A
aMMP-8 levels were determined by IFMA, and chair-side dip-stick was performed
29 subjects, age not applicable
Healthy, gingivitis, and chronic periodontitis
aMMP-8 GCF levels and chair-side test differentiated periodontitis from gingivitis, and healthy control sites. Scaling and root planing could be followed successfully by both PoC-/chair-side and IFMA
5
The effect of adjunctive low-dose doxycycline therapy on clinical parameters and GCF MMP-8 levels in chronic periodontitis [25]
To compare effectiveness of LDD combined with nonsurgical periodontal therapy alone in reducing levels of MMP-8 in GCF and improving clinical parameters in patients with chronic periodontitis
GCF
12 nonsmokers. none of the subjects was a heavy smoker (i.e., not more than 10 cigarettes/day)
aMMP-8 levels determined by the immunofluorometric assay
30 subjects, 37 to 61 years of age
Chronic periodontitis
Randomized, double blind, placebo-controlled, parallel arm study. LDD improved the effects of nonsurgical periodontal therapy
6
Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in GCF from periodontitis-affected patients [26]
Assessment of periodontal disease performed through measurement of extracellular MMP-8, MMP-9, and their TIMP-1 and TIMP-2 in GCF
GCF samples
N/A
aMMP-8 levels were determined by immune-western blotting (Cat. MAB 3316, Chemicon International, Temecula, CA, USA), MMP-9 by zymography, and dot blot of TIMP-1 and TIMP-2 (Cat. sc-6832 and sc-6835, respectively, Santa Cruz Biotechnology, Santa Cruz, CA, USA)
24 subjects, 30 to 35 years old
Healthy, and chronic periodontitis
A different pattern of aMMP-8 in control and patient site was found. The study has established the significant correlation between the severity of periodontal disease and the actual aMMP-8. aMMP-8 and the low level of both TIMP-1 and TIMP-2 were found
7
Is the excessive inhibition of matrix metalloproteinases (MMPs) by potent synthetic MMP inhibitors (MMPIs) desirable in periodontitis and other inflammatory diseases? That is: “Leaky” MMPIs vs excessively efficient drugs [27]
Comparison between SDD and tetracycline (non-antibacterial composition) with more potent MMP inhibitors
N/A
N/A
N/A
N/A
N/A
Letter to editor: beneficial clinical efficiency observed only with LDD
8
Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side test [28]
To evaluate the efficacy of the aMMP-8-specific chair-side dip-stick test in longitudinally monitoring the periodontal status of smoking and nonsmoking patients with chronic periodontitis, using aMMP-8 concentration in GCF
GCF samples
11 smokers and 5 nonsmokers were included in the study
aMMP-8 levels were determined by chair-side lateral-flow immunotests and IFMA
16 subjects, age not applicable
chronic periodontitis
Persistently elevated GCF aMMP-8 concentration were identified, and they indicated sites at enhanced risk; patients with inadequate response to conventional treatment were identified by PoC/chair-side test and IFMA
9
Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation [3]
To determine the correlation between salivary biomarkers specific for periodontal tissue inflammation, collagen degradation, bone turnover, and clinical features of periodontitis
Unstimulated whole expectorated saliva samples
33.3 case subjects and 27.6 control subject smokers were included in the study
Total MMP-8 levels were determined by the ELISA kit (Quantikine, R&D Systems, minneapolis, MN, USA)
57 subjects, 28 to 61 years of age
Healthy, and chronic periodontitis
A salivary level of MMP-8 appears to serve as biomarker of periodontitis
11
Characteristics of collagenase-2 from gingival crevicular fluid and peri-implant sulcular fluid in periodontitis and peri-implantitis patients: pilot study [30]
To identify the difference in collagenolytic activity between healthy subjects and subjects with peri-implantitis and to find the correlation between severity of peri-implantitis and collagenase activity
GCF and PISF samples
Nonsmokers were included in the study
Both aMMP-8 and total MMP-8 levels were determined by western blot and DNP-octapeptide assay
29 subjects, 4 healthy, 5 gingivitis patients, 10 chronic periodontitis patients, 5 implants patients, 5 peri-implantitis patients, the age range 23 to 72 years old
Healthy, gingivitis, chronic periodontitis and peri-implantitis
Peri-implantitis PISF contained higher active aMMP-8 levels and activity than GCF from similar deep chronic periodontitis sites. GCF and PISF from severe chronic periodontitis and peri-implantitis exhibited the highest aMMP-8 from PMNs and fibroblasts
12
Host-response therapeutics for periodontal diseases [31]
To figure out the MMP-1, -2, -3, -8, -9, -12, and -13 levels in a cohort of African American children with and without aggressive periodontitis
GCF samples
17 nonsmokers were included in the study
Total MMP-1, -2, -3, -8, -9, -12, and -13 levels were determined by the ELISA kit (SenzoLyte 520, AnaSpec, San Jose, CA, USA)
44 subjects with AgP, 7 to 19 years of age, and 12 healthy controls. 17 adults with chronic periodontitis 35 to 65 years of age
Healthy, chronic periodontitis, and aggressive periodontitis
MMP-8 levels were elevated in AgP sites relative to nondiseased sites in the same subjects, in siblings and controls and subjects with chronic periodontitis. MMPs associated with the AgP sites in children were generally elevated compared to an adult cohort with a history of chronic periodontitis
15
Matrix metalloproteinase-8 concentration in shallow crevices associated with the extent of periodontal disease [34]
To study association between MMP-8 levels in shallow, gingival crevices and the extent of periodontal disease
GCF samples
20 nonsmokers and 28 smokers were included in the study
Total MMP-8 levels were determined by the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA)
48 subjects, 22 to 75 years old
Chronic periodontitis
Statistically significant association between MMP-8 concentration from shallow crevices and the extent of attachment level (AL) ≥ 4 mm () and AL ≥ 6 mm (), in subjects with moderate to high plaque scores
16
Identification of pathogen and host-response markers correlated with periodontal disease [35]
To find out the ability of putative host and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm
Unstimulated whole saliva samples
0% healthy, 19% gingivitis, 36% mild chronic periodontitis, and 81% severe chronic periodontitis smokers were included in the study
Total MMP-8 and -9, calprotectin, and OPG levels were determined by the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA). A.actinomycetemcomitans, C. rectus, F. nucleatum, P. intermedia, P. gingivalis, T. forsythia, and T. denticola with a quantitative PCR assay, IL-1β, -2, -4, -5, -6, -10, and -13, TNF-α, (FN-γ by protein microarray (Whatman, Florham Park, NJ), and ICTP by radioimmunoassay (Immunodiagnostic Systems, Fountain Hills, AZ)
100 subjects, aged ≥ 18 years old
Healthy, gingivitis, and chronic periodontitis
Multiple combinations of biomarkers especially MMP-8, 9, and osteoprotegerin combined with red complex bacteria provided highly accurate predictions of periodontal diseases.
17
Association of GCF biomarkers during periodontal maintenance with subsequent progressive periodontitis [36]
To detect potential markers of advanced periodontitis in saliva. In addition, we compared two MMP-8 detection methods using IFMA and ELISA to differentiate periodontitis subjects from controls
Stimulated whole saliva samples
17.2% healthy and 52.3% chronic periodontitis smokers were included in the study
aMMP-8 levels were determined by IFMA, total MMP-8, MMP-14, and TIMP-1 levels were determined by the ELISA kit (Amersham, GE Healthcare, Buckingamshire, UK) and ICTP levels were measured by enzyme immunoassay (Orion Diagnostica Oy, Espoo, Finland)
165 subjects, aged ≥ 30 years old
Healthy and chronic periodontitis
Salivary aMMP-8, when used in combination with TIMP-1 and ICTP is a potential biomarker in the detection of advanced periodontitis. The detection of total MMP-8 by the traditional ELISA method technique is less accurate than the aMMP-8 IFMA technique
19
Associations between matrix metalloproteinase-8 and -14 and myeloperoxidase in gingival crevicular fluid from subjects with progressive chronic periodontitis: a longitudinal study [13]
To associate the levels, molecular forms, isoenzyme distribution, and degree of activation of MMP-8 and MMP-14, MPO, and TIMP-1 in GCF from patients with progressive periodontitis at the baseline and after periodontal therapy
GCF samples
N/A
aMMP-8 levels were determined by western blot and IFMA. MPO levels were determined by the ELISA kit (Immundiagnostik, Bensheim, Germany). MMP-14 and TIMP-1 levels were determined by the ELISA kit (Biotrak, GE healthcare, amersham, Slough, UK)
25 subjects, 35 to 62 years old
Chronic periodontitis
High aMMP-8 and MPO levels and a high MPO/MMP-8 positive correlation were found in active and inactive sites at baseline. After treatment, decreases in MPO and aMMP-8 were seen, except for active sites in which MMP-8 differences were not significant
To investigate the association between salivary aMMP-8 and PMN elastase with commonly used periodontal health indices in a birth cohort of adolescents accounting for their smoking habits
Stimulated whole saliva samples
61 boys and 66 girls were smokers. 197 boys and 177 girls were nonsmokers
Active MMP-8 levels were determined by IFMA
501 subjects, 15 to 16 years old
Most subjects were chronic periodontitis
Smoking significantly decreased both biomarkers, including aMMP-8 studied
21
Detection of gingival crevicular fluid MMP-8 levels with different laboratory and chair-side methods [6]
To compare four methods for detection of MMP-8 in GCF
GCF samples
Smokers were included in the study, but exact number of smokers is not mentioned
aMMP-8 levels were determined by DentoAnalyzer (Dentognostics GmbH, Jena, Germany), IFMA, and chair-side lateral-flow immunotests (Medix Biochemica Ltd, Espoo, Finland).Total MMP-8 levels were determined by the ELISA kit (Amersham, GE healthcare, Buckingamshire, UK)
10 subjects, age not applicable
Healthy, gingivitis and chronic periodontitis
IFMA (aMMP-8) and DentoAnalyzer (aMMP-8) results can detect MMP-8 from GCF samples, and these methods are comparable. The chair-side dip-stick test (aMMP-8) results were well in line with these assays. The Amersham ELISA (total MMP-8) results were not in line with tests.
22
Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy [39]
To compare the levels of MMP-8, MMP-9, TIMP-1, TIMP-2, and MPO in GCF of chronic periodontitis patients and controls at the baseline and three months after nonsurgical therapy
GCF samples
N/A
Total MMP-8, MMP-9, TIMP-1, and TIMP-2 levels were determined by the ELISA kit (DuoSet R&D Systems, Inc., Minneapolis, MN, USA), and MPO levels were determined (Sigma chemical, Co., St. Louis, MO, USA)
42 subjects, 35 to 55 years old
Healthy, and chronic periodontitis
Level of all the markers except TIMP-1 was found to be higher in GCF of patients compared with controls. The elevated level decreased three months after periodontal therapy
23
Use of host-and bacteria-derived salivary markers in detection of periodontitis: a cumulative approach [40]
The salivary concentration of three different salivary markers P. gingivalis, IL-1β, and MMP-8 were calculated together to obtain the cumulative risk score for detection of periodontitis
Stimulated whole saliva samples
N/A
P. gingivalis with a quantitative real-time PCR assay, IL-1β levels were determined by the ELISA kit (Amersham), and aMMP-8 levels were determined by IFMA
165 subjects, aged ≥ 30 years old
Healthy, and chronic periodontitis
The results point to that a cumulative risk score, calculated from the three salivary biomarkers, detects periodontal status more accurately than any of the markers individually. However, it is still sufficient to distinguish the periodontitis patient from the healthy group. However, aMMP-8 is reliable when used alone
24
Smoking and matrix metalloproteinases, neutrophil elastase and myeloperoxidase in chronic periodontitis [41]
To investigate the possible relationship between smoking and serum concentration of aMMP-8, MMP-9, TIMP-1, MPO, and neutrophil lactase in chronic periodontitis patients relative to periodontally healthy subjects
Serum samples
Healthy subjects (17 smokers) and chronic periodontitis patients (16 smokers) were included in the study
aMMP-8 levels were determined by IFMA; MMP-9 levels were determined by Biotrak ELISA Systems, Amersham Biosciences Ltd, Buckinghamshire, UK; TIMP-1 levels were measured by Duoste ELISA Development Systems, R&D systems, MN, USA; MPO levels were measured by Immunodiagnostic AG, Bensheim, Germany; and neutrophil elastase by Bender MedSystems GmbH, Vienna, Austria
111 subjects, 33 to 65 years
Healthy, and chronic periodontitis
aMMP-8 concentration and aMMP-8/TIMP-1 molar ratios in chronic periodontitis group were not found to be significantly different from those in the periodontally healthy group
25
Oral rinse MMP-8 point-of-care immuno test identifies patients with strong periodontal inflammatory burden [42]
To determine if MMP-8 (measured by three different methods), TIMP-1, and elastase activity differentiate subjects with the different periodontal conditions, and second, to find out if MMP-8 levels were comparable among the methods used
Oral-rinse samples
Smokers were included in study, but the exact number of smokers is not mentioned
aMMP-8 levels were determined by DentoELISA (Dentognostics GmbH, Jena, Germany) and IFMA; total MMP-8 levels were measured by the ELISA kit (Amersham, GE Healthcare, Buckingamshire, UK); TIMP-1 levels were determined by the ELISA kit (Amersham); and elastase activity by Sigma Co., St Louis, MO, USA
214 subjects, 44 to 78 years old
Chronic periodontitis
aMMP-8 testing of oral-rinse samples may be beneficial in periodontal diagnostics. Total MMP-8 levels were not useful in diagnosis
26
Salivary biomarkers of periodontal disease in response to treatment [43]
To check utility of salivary biomarkers in the monitoring of periodontal disease over time in subjects who received localized periodontal therapy
Unstimulated whole saliva samples
23% of the SRP group, and 33% of the OHI group smokers were included in the study
Total MMP-8 and OPG levels were determined by the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA) and IL-1β, IL-8, MIP-1α, and TNF-α levels were measured by Luminex human cytokine/chemokine multiplex kits (Millipore, St. Charles, MO, USA)
68 subjects, aged ≥ 18 years old
Chronic periodontitis
Salivary levels of biomarkers, i.e., IL-1β MMP-8, OPG, and MIP-1α reflected disease severity and response to therapy suggesting their potential utility for monitoring periodontal disease status
27
Full-mouth profile of active MMP-8 in periodontitis patients [44]
To investigate whether there was a relationship between clinical diagnostic parameters and the concentration of aMMP-8 in GCF in the site level full-mouth analysis
GCF samples
Nonsmokers were included in the study
aMMP-8 levels were determined by IFMA
9 subjects, 35 to 66 years old
Chronic periodontitis
A statistically significant relationship found between level of aMMP-8 and pocket depth
28
Matrix metalloproteinase-8 is the major potential collagenase in active peri-implantitis [45]
To compare levels of MMP-1, -8, and -13 in PISF of both healthy and diseased sites and to find correlation between these MMPs with bone loss
PISF samples
N/A
Total MMP-8, MMP-1, and MMP-13 levels were determined by Fuji Chemical Industry, Takaoka, Japan
64 subjects, the aged range 59 to 78 years old
Peri-implantitis
This study also showed MMP-8 as a possible marker for progressive bone loss in peri-implantitis
29
Matrix metalloproteinases and inflammatory cytokines in oral fluid of patients with chronic generalized periodontitis and various construction materials [46]
To compare oral fluid of practically healthy subjects with intact periodontium and patient with chronic generalized periodontitis with various structural materials of dental restorations
Oral fluid samples
N/A
Total MMP-8 levels were determined by the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA)
105 subjects, 18 to 52 years old
Chronic periodontitis
The MMP-8 level in oral fluid was found to be higher than the normal only in patients with chronic generalized periodontitis with metal restorations. No significant difference was found in the level of MMP-8 in patients of chronic generalized periodontitis without metal restoration
30
Effect of scaling and root planing on interleukin-1β, interleukin-8 and MMP-8 levels in gingival crevicular fluid from chronic periodontitis patients [47]
To determine amounts of MMP-8, IL-8, and IL-1β in GCF from patients with chronic periodontitis in relation to clinical parameters
GCF samples
Nonsmokers were included in the study
Total MMP-8 and IL-8 and IL-1β levels were determined by the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA)
51 subjects, 30 patients (mean age 48.7 ± 9.1 years old), and 21 healthy subjects (mean age 33.7 ± 8.2 years)
Healthy, and chronic periodontitis
Short-term nonsurgical therapy resulted in significant improvement in periodontal indices and a marked decrease of MMP-8, IL-8, and IL-1β in GCF. However, the level of humoral factors was still higher than those in control group
31
Associations of periodontal microorganisms with oral salivary proteins and MMP-8 in gingival crevicular fluid [19]
To investigate in subjects with and without periodontitis, the levels of salivary proteins and aMMP-8 in GCF in relation to the presence of specific periodontal pathogens
Unstimulated and stimulated whole saliva, and GCF samples
15 healthy, and 30 chronic periodontitis smokers were included in the study
aMMP-8 levels were determined by IFMA, A.actinomycetemcomitans, P. intermedia, P. gingivalis T. forsythia, and T. denticola with a quantitative PCR assay; Albumin was analyzed using an immunoturbidometric Tina-Quant® kit (Roche, Basel, Switzerland); the salivary immunoglobulin concentrations were then analyzed by ELISA [87]; and salivary total protein was measured using the colorimetric Lowry method [49]
101 subjects, mean age 59.2 ± SD 2.9
Healthy, and chronic periodontitis
Salivary albumin and protein concentration were significantly higher in subjects with T. denticola. Level of aMMP-8 was significantly higher in subjects with T. denticola and T. forsythia
32
Treponema denticola associates with increased levels of MMP-8 and MMP-9 in gingival crevicular fluid [50]
To assess the association between the presence of site-specific subgingival microorganisms and the level of aMMP-8 and MMP-9 in GCF
GCF samples
15 healthy and 30 chronic periodontitis were included in the study
aMMP-8 levels were determined by IFMA, A.actinomycetemcomitans, P. intermedia, P. gingivalis, T. forsythia, and T. denticola with a quantitative PCR assay; MMP-9 levels were determined by the ELISA kit (Amersham, Biosciences UK Ltd, Buckinghamshire, UK)
99 subjects, mean age 59.2 ± 2.9
Healthy, and chronic periodontitis
The presence of T. forsythia and T. denticola was associated with increased levels of aMMP-8 in the test sites
33
Cytokine and matrix metalloproteinase expression in fibroblasts from peri-implantitis lesions in response to viable porphyromonas gingivalis [51]
To analyze inflammatory reactions of fibroblasts after in vitro challenge with P. gingivalis
Fibroblasts
All subjects’ nonsmokers were included in the study
Total MMP-8, -1 levels were determined by the ELISA kit (Quantikine Human, Pharmacia Biotech, Buckinghamshire, UK), TIMP-1 immunoassay (R&D Systems, Minneapolis, MN, USA), and P. gingivalis with a quantitative real-time PCR assay
Five patients periodontally healthy 54.4 ± (±18.7) years old, nine patients (II) 57.8 (±12.4) years old, seven peri-implantitis patients 54.4 (±9.2) years old
Peri-implantitis
Fibroblasts from peri-implantitis and periodontitis lesions gave a more pronounced inflammatory response to the P. gingivalis challenge than fibroblasts from healthy donors. They may therefore be involved in the development of inflammation in peri-implantitis and periodontitis. Moreover, the sustained upregulation of inflammatory mediators and MMP-1 in peri-implantitis fibroblasts may play a role in the pathogenesis of peri-implantitis
34
Salivary biomarkers of oral health: a cross-sectional study [52]
Aimed to investigating if known salivary biomarkers could be used for epidemiological studies for detection of periodontitis
Stimulated whole saliva samples
75 smokers were included in the study
Active MMP-8 levels were determined by IFMA; TIMP-1 levels were measured by the ELISA kit; (Amersham); TNF-α, IL-1β, IL-6, and IL-8 were measured by Luminex Chemokine multiplex); lysozyme levels were measured the ELISA kit (Quantikine, R&D Systems, Minneapolis, MN, USA)
966 subjects, 20 to 89 years old
Chronic periodontitis
aMMP-8 could be used as marker of periodontal disease in more significant patient populations
35
Oral salivary type I collagen degradation end-products and related matrix metalloproteinases in periodontitis [53]
Type I collagen degradation end products and related MMPs were examined aiming at detecting potential markers of periodontitis in saliva with high sensitivity and specificity
Stimulated whole saliva samples
86 smokers were included in the study
Active MMP-8 levels were determined by IFMA; MMP-9 and MMP-13 levels were measured by the ELISA kit (Amersham, GE Healthcare, Buckinghamshire, UK); TRACP-5b levels were measured by BoneTRAP® assay, Immunodiagnostic Systems Ltd, Boldon, UK); ICTP levels were measured by enzyme immunoassay; (Orion Diagnostica UniQ ICTP, EIA; Orion Diagnostica, Espoo, Finland); CTx levels were measured by Serum CrossLaps® ELISA assay (Immunodiagnostic, Systems Ltd, Boldon, UK); and NTx levels were measured by OSTEOMARK® NTx; serum levels were measured by Wampole Laboratories (Princeton, NJ, USA)
230 subjects of ≥30 years old
Chronic periodontitis
aMMP-8 is a reliable biomarker candidate for detecting alveolar bone destruction
To evaluate MMP-1, -2, -3, -8, -9, -12 and -13 levels in the GCF after treatment of LAgP and to correlate these levels with clinical response
GCF samples
Nonsmokers were included in the study
Total MMPs levels were determined by the ELISA kit (SensoLyte 520, AnaSpec, Fremont, CA)
29 subjects of 5 to 21 years old
Aggressive periodontitis
Treatment of LAgP with Conventional mechanical treatment and systemic antibiotics reduced specific MMPs levels effectively. The significant association was observed between MMP-1, -2, -3, -8, -9, -12 and -13 and percentage of sites with PD > 4 mm
37
Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health [55]
To determine to analyze expression levels in unstimulated whole saliva samples collected from multiple occasions from 30 healthy adults and 50 chronic adult periodontitis patients
Unstimulated whole saliva samples
Only nonsmokers were included in study
Total MMP-8 levels were determined by the ELISA kit (Quantikine, R&D Systems, minneapolis, MN, USA)
80 subjects of 18 to 45 years old
Healthy and chronic periodontitis
Salivary levels of MMP-8 were significantly elevated in periodontitis patients compared with the daily variation observed in healthy adults
38
Clinical correlates of a lateral-flow immunoassay oral risk indicator [18]
To investigate the clinical correlates of a lateral-flow immunoassay with BOP, oral hygiene, and periodontal probing depth on the first time
Oral-rinse samples
5 smokers and 71 nonsmokers were included in the study
aMMP-8 levels were determined by chair-side lateral-flow immunotests (Dentognostics GmbH, Jena, Germany)
76 subjects, age not applicable
Healthy, and chronic periodontitis
The chair-side aMMP-8 immunoassay showed a high (82.6%) sensitivity for at least two sites with BOP and periodontal pockets. It showed a lower relationship with single-site periodontal pockets and BOP
39
Crevicular fluid biomarkers and periodontal disease progression [56]
The primary aim was to compare the concentrations of IL-1β, IL-6, PGE2, MMP-8, and MIP-1α in the whole saliva from patients with gingivitis with concentrations of these substrates in the saliva of patients with a clinically healthy periodontium
Unstimulated whole saliva samples
N/A
Total MMP-8, IL-1β, IL-6, PGE2, and MIP-1α levels were determined by ELISA kit, assay design, Ann Arbor, MI & EMD, millipore, Billerica, MA
80 subjects of 23 to 38 years old
Healthy and gingivitis
Concentrations of IL-1β, IL-6, and MMP-8 cannot distinguish gingivitis from health
41
Oral salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis [58]
To investigate the association of selected salivary biomarkers with periodontal parameters and validate the use of a novel salivary diagnostic approach, the cumulative risk score (CRS), in detection of periodontitis in subjects with angiographically verified coronary artery disease diagnosis
Stimulated whole saliva samples
58 were current smokers and 202 former smokers were included in the study
aMMP-8 levels were determined by IFMA, IL-1β was measured by flow cytometry-based Luminex kits, Milliplex, Map Kit; MPXHCYTO-60k, Millipore, Billerica, MA, USA, and P. gingivalis with a quantitative PCR assay was performed
493 subjects, age nonapplicable
Chronic periodontitis
The high salivary concentration of aMMP-8, IL-1β, and P. gingivalis was associated with deepened periodontal pockets and alveolar bone loss. aMMP-8 performed better compared to BOP%
42
Matrix metalloproteinases and myeloperoxidase in GCF provide site-specific diagnostic value for chronic periodontitis [59]
To identify the diagnostic accuracy of GCF candidate biomarkers to discriminate periodontitis from inflamed and healthy sites and to compare the performance of two independent MMP-8 immunoassays
GCF samples
5 subjects healthy (nonsmokers), 3 nonsmokers with gingivitis, and 3 nonsmokers with chronic periodontitis were included in the study
aMMP-8 levels were determined by IFMA, and total MMP-8 was measured by ELISA kits, GE Healthcare, Amersham
MMPs are highly discriminatory biomarkers for site-specific diagnosis of periodontitis. The comparison of two quantitative MMP-8 methods demonstrated IFMA to be more accurate than ELISA
43
Gingival crevicular fluid matrix metalloproteinase-8 levels predict treatment outcome among smokers with chronic periodontitis [60]
To explore different GCF aMMP-8 patterns in smokers and nonsmokers with chronic periodontitis and test the utility of baseline GCF aMMP-8 levels in predicting categorically assessed treatment outcomes
GCF samples
10 smokers and 5 nonsmokers were included in the study
aMMP-8 levels were determined by IFMA
15 subjects, aged 28 to 64 years
Chronic periodontitis
Baseline aMMP-8 level in GCF strongly predicts how aMMP-8 levels behave during the maintenance period. In this regard, aMMP-8 analysis can be considered more useful than BOP. In smokers’ sites, high baseline aMMP-8 levels indicate and predict weak treatment response
44
Targeted salivary biomarkers for discrimination of periodontal health and disease(s) [61]
To evaluate sensitivity and specificity of a chair-side test for aMMP-8 to detect periodontitis
Oral-rinse samples
25 smokers were included in the study
aMMP-8 levels were determined by chair-side lateral-flow immunotests, Dentognostics GmbH, Jena, Germany
60 subjects, aged ≥ 18 years
Healthy and chronic periodontitis
Positive results of the aMMP-8 test significantly correlate with generalized chronic periodontitis. The test shows 87% sensitivity and 60% specificity in the diagnosis of chronic periodontitis
46
The utility of gingival crevicular fluid matrix metalloproteinase-8 response patterns in prediction of site-level clinical treatment outcome [63]
To study different response patterns of MMP-8 among smoker and nonsmoker subjects with CP and GAgP to test its utility in predicting site level treatment outcome
GCF samples
86 smokers were included in the study
aMMP-8 levels were determined by IFMA
158 subjects, aged 27 to 49 years
Chronic periodontitis and aggresive periodontitis
Distinct types of MMP-8 response patterns were obtained for smokers and nonsmokers. Optimal cutoff levels of aMMP-8 defined for smokers and nonsmokers, which indicate risk for compromised treatment outcome at baseline and during maintenance
47
Pilot study on oral health status as assessed by an active matrix metalloproteinase-8 chair-side mouth rinse test in adolescents [64]
To investigate whether a PoC mouth rinse test based on aMMP-8 immunoassay could identify patients with oral inflammatory burden among adolescents with early pathologic findings
Mouth rinse samples
5 smokers, and 42 nonsmokers were included in the study
aMMP-8 levels were determined by chair-side lateral-flow immunotests (Dentognostics GmbH, Jena, Germany)
47 subjects, aged 15 to 17 years
Chronic periodontitis
PoC/chairside was found to be useful in the online detection/diagnosis of oral inflammatory burden, i.e., periodontitis in adolescents with early, initial signs of periodontitis. Detection of caries is also possible but with less efficiency. The test shows 76.5% sensitivity and 96.7% specificity in the diagnosis of initial chronic periodontitis
48
Host-derived biomarkers at teeth and implants in partially edentulous patients. A 10-year retrospective study [65]
To compare host-derived biomarkers in PISF and in GCF from adjacent teeth and to analyze their level in both periodontal disease and healthy condition
PISF and GCF samples
Smokers were included in study but exact number of smokers is not mentioned
IL-1β, MMP-3, MMP-8, MMP-1, and MMP-1/TIMP-1 levels were determined by ELISA kits, R&D systems, Europe Ltd, Abingdon, UK
Total 997 samples were evaluated
chronic periodontitis and peri-implantitis
Increased levels of MMP-8 and IL-1β in PISF or GCF may be associated with inflammation around teeth and implants while lower levels of MMP-8/TIMP-1 may be an indicator of disease progression around implants and eased levels of MMP-8 and IL-1β in PISF or GCF may be associated with inflammation around teeth and implants while lower levels of MMP-1/TIMP-1 may be an indicator of disease progression around implants
49
Non-antibacterial tetracycline formulations: host-modulators in the treatment of periodontitis and relevant systemic diseases [66]
To address the evidences supporting adjunctive use of host modulation therapy with scaling and root planning in the long-term management of periodontal disease
N/A
N/A
N/A
N/A
N/A
Review: aMMP-8 PoC test is suitable to monitor the adjunctive beneficial SDD in periodontitis
50
Analysis of matrix metalloproteinases, especially MMP-8, in GCF, mouth rinse, and saliva for monitoring periodontal diseases [7]
To assess diagnostic ability of biomarkers when combined with microbial profiles
PICF samples
4 current smokers and 21 past smokers were included in the study
Total MMP-8, OPG, IL-1β, TIMP-2, and vascular endothelial growth factor levels were determined by ELISA kits, custom human Quantibody, arrays, RayBiotech, Inc., Norcross, GA, USA, and A.actinomycetemcomitans, P. intermedia, P. gingivalis, T. forsythia, and T. denticola with a quantitative PCR assay
68 subjects, age range: 37 to 83 years
Peri-implantitis
The present data suggest that the increased levels of the selected PICF-derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site-specific microbial profiles may be associated with peri-implantitis and could have potential as predictors of peri-implant diseases
aMMP-8 levels increase in peri-implantitis affected implants both in nonperiodontitis and periodontitis patients, but levels still after treatment of the condition reflect intensified host response around implants and indicate challenges of controlling peri-implantitis with any treatment modality
53
Correlation between peri-implant sulcular fluid rate and expression of collagenase2 (MMP8) [68]
To identify correlation between PISF and collagenase-2 level in superficial and fundus area of PI sulcus
PISF samples
N/A
aMMP-8 levels were determined by DentoELISA immunoassay (Dentognostics, Jena, Germany)
15 subjects, the age range 43 to 75 years
Peri-implantitis
Examination of aMMP-8 is a sensitive method when examining early inflammatory changes but depends from the depth of the sample collection in the gingival pocket
54
Rapid assessment of oral salivary MMP-8 and periodontal disease using lateral flow immunoassay [15]
To determine the efficacy of a novel POCID for detecting MMP-8 concentration in oral fluids in comparison with a gold standard laboratory-based immunoassay
Unstimulated whole saliva samples
10 smokers were included in the study
Total MMP-8 levels were determined by rapidassays, ApS, Copenhagen-S, Denmark, EMD Millipore, Billerica, MA and luminex, Austin, TX, USA
41 subjects, aged 18 years or older
Healthy and chronic periodontitis
MMP-8 can be detected by POCID and concentration correlates with luminex for both saliva and rinse fluids. This study confirmed and further extended the original studies of Nwhator et al. [18] and Heikkinen et al. [64]
55
Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: An exploratory study [69]
Assessment of level and diagnostic accuracy of an asset of potential biomarkers in GCF from patients with chronic periodontitis and AAP
GCF samples
19 smokers were included in the study
aMMP-8 levels were determined by IFMA, MPO levels were determined by ELISA kit, immunodiagnostik, AG, Bensheim, Germany. IL-1β, IL-6, TNF-α, Dkk-1, ON, PTN, TRAP-5, and OPG levels were determined by Multiplex detection panels Millipore, St. Charles, MO, USA, Magpix, Millipore, St. Charles, MO, USA, and MMP-2 and -9 levels were determined by gelatin zymography.
106 subjects, aged 44 to 52 years
Chronic periodontitis
aMMP-8 shows diagnostic potential for both chronic periodontitis and AAP. aMMP-8 was found to be higher in chronic periodontitis, followed by AAP
56
Pilot study on the genetic background of an active matrix metalloproteinase-8 test in finnish adolescents [70]
To determine whether aMMP-8 chair-side test can detect initial periodontitis and caries with genetic background in adolescents
Oral fluid and DNA samples
5 smokers and 42 nonsmokers were included in the study
aMMP-8 levels were determined by chair-side lateral-flow immunotests (Dentognostics GmbH, Jena, Germany)
47 subjects aged 15 to 17 years
Chronic periodontitis
The aMMP-8 chair-side test has potential to detect initial periodontitis in adolescents with predisposing genetic background. aMMP-8 PoC/chair-side test acts as a gene test
57
Association of oral fluid MMP-8 with periodontitis in swiss adult subjects [12]
To find association between periodontitis and levels of aMMP-8 in saliva and GCF
Stimulated whole saliva and GCF
Never smokers were 150 (58.1%). Former smokers were 70 (27.1%). Current smokers were 38 (14.7%)
aMMP-8 levels were determined by IFMA
258 subjects, mean age 43.5 (21–58) years
Healthy and chronic periodontitis
Elevated levels of aMMP-8 in saliva and GCF are significantly associated with periodontitis in a systemically healthy adult
58
Association between serum and oral matrix metalloproteinase-8 levels and periodontal health status association between serum and oral matrix metalloproteinase-8 levels and periodontal health status association between serum and oral matrix metalloproteinase-8 levels and periodontal health status [71]
To identify the association between extent of circulating aMMP-8 and status of periodontal disease and aMMP-8 levels in oral fluids
Unstimulated whole saliva, stimulated whole saliva, GCF, and serum samples
Smokers were included in study but exact number of smokers is not mentioned
aMMP-8 levels were determined by IFMA, PerioSafe plus, (Dentognostics GmbH, Jena, Germany), and A.actinomycetemcomitans, P. intermedia, P. gingivalis, T. forsythia, and T. denticola with a semiquantitative PCR assay
59 subjects, aged 23 to 58 years
Healthy, gingivitis, and chronic periodontitis
The serum levels correlated significantly with oral aMMP-8 as well as with clinical periodontal parameters in a dose-dependent manner in systematically healthy subjects
59
Influence of different forms and materials (zirconia or titanium) of abutments in peri-implant soft-tissue healing using matrix metalloproteinase-8: a randomized pilot study [72]
To compare peri-implant connective tissue response around titanium and zirconia abutments
PISF samples
Nonsmokers were included in the study
Total MMP-8 levels were determined by ELISA, Boster Biological Technology Co Ltd
12 subjects, the age range 20 to 45 years
Healthy
This study suggests the presence of more remodeling and/or inflammatory phenomena around titanium implant abutments than around zirconia abutments of a different design during the early stages but not at 1 year
60
Microbiological and aMMP-8 findings depending on peri-implant disease in patients undergoing supportive implant therapy [73]
To study relation of microbiological findings and aMMP-8 level with peri-implant mucositis and peri-implantitis in subjects receiving periodontal or implant therapy
PISF samples
17 smokers with 43 implant sites
aMMP-8 levels were determined by DentoELISA (Dentognostics GmbH, Jena, Germany)
89 subjects with 171 implants. Mean age: 52 ± years, 116 dental implants were healthy, 39 dental implants had mucositis, and 16 dental implant had peri-implantitis
Peri-implantitis, peri-mucositis around implants, and chronic periodontitis
Within the limitations of this study, microbiological findings and aMMP-8 levels are not suitable for a differentiation between healthy, peri-mucositis, and peri-implantitis in patients all undergoing SIT/SPT. No healthy and disease patients without SIT/SPT were involved. Only smoking and the presence of Pi appear to be potential parameters associated with peri-implant disease in SIT/SPT patients. SIT/SPT intervention downregulated aMMP-8 during maintenance
61
Diagnosing peri-implant disease using the tongue as a 24/7 detector [49]
Anyone, anywhere, and anytime diagnostics were developed for peri-implant disease. The sensors responded to MMPs and provided proof of concept in statistically differentiating patients with peri-implant disease from healthy volunteers
Oral fluid
No-smokers were included in the study
aMMP-8 levels were determined by DentoELISA (Dentognostics GmbH, Jena, Germany) and MMP-8 analyzed by 24/7 chewing gum
33 subjects saliva or sulcus fluid collected from patients with peri-implant disease (defined as mucositis or peri-implantitis; ) and healthy control ()
Peri-implantitis
Elevated MMP-8 could be detected in peri-implantitis, oral fluid vs. healthy oral fluid
